高盐及低盐饮食对人外周血单核细胞亚群表型的动态影响及相关机制
|
摘要
研究目的：高盐饮食(high salt diet, HS)不仅是高血压的致病因素,还能独立于血压水平造成靶器官损害。炎症反应是靶器官损害的中心环节,而单核／巨噬细胞是引发靶器官炎症反应的主要细胞类型。近年来研究显示,单核细胞由三个亚群组成(经典型,CD14++CD16单核细胞[Monl];中间型,CD14++CD16+单核细胞[Mon2]；非经典型,CD14+CD16++单核细胞[Mon3])。不同亚群的单核细胞具有不同的生理和病理生理学作用。其中CD14++CD16+型单核细胞被认为是“促炎症型单核细胞”,与动脉粥样硬化(atherosclerosis, AS)的形成密切相关。此外,单核细胞还可与血小板结合形成单核细胞-血小板聚集体(monocyte-platelet aggregates, MPA),通过相互作用共同参与多种病理过程。高盐饮食是否能够对单核细胞表型以及MPA的形成产生影响,进而通过增加“促炎症型单核细胞”的数量和MPA的形成来加重靶器官损害,尚未见到相关报道。因此,本研究旨在对健康志愿者进行不同食盐含量的饮食干预,观察食盐摄入量的变化对外周血单核细胞亚群表型的动态影响,并探讨其相关机制。
研究内容与方法：共纳入健康志愿者22人。男性10人,平均30.10±2.99岁；女性12人,平均29.40±2.65岁。先后给予高盐饮食(15g/d)7天和低盐饮食(5g/d)7天。所有饮食均由研究组提供,并在同一地点进餐。在基线最后一天、高盐饮食第一天、高盐饮食第七天、低盐饮食第三天、低盐饮食第七天收集24小时尿。分别在基线最后一天,高盐饮食第二天、高盐饮食第七天、低盐饮食第二天,低盐饮食第七天采集受试者外周血进行单核细胞亚群和MPA的流式细胞术(flow cytometry, FCM)检测,对单核细胞表型和血小板标志分子CD14.CD16,CD86和CD41进行四色分析。对基线最后一天,高盐第七天和低盐第七天采集外周血使用密度梯度离心法分离外周血单个核细胞(peripheral blood mononuclear cell, PBMC),并采用磁性细胞分选技术(magnetic activated cell sorting, MACS)以CD14阳性分选免疫磁珠纯化单核细胞。使用TRIzol试剂裂解纯化后的单核细胞,提取总RNA;采用实时荧光定量聚合酶链反应(Real-TimePCR)对单核细胞炎症相关因子和炎症抑制因子的基因表达水平进行检测,包括：C-C趋化因子配体5(CCL5)、C-C趋化因子受体5(CCR5)、单核细胞趋化因子-1(MCP-1)、C-C趋化因子受体2(CCR2)、转化生长因子-β(TGF-β)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、C-X3-C趋化因子受体1(CX3CR1).精氨酸酶-1(Arg-1)、P选择素糖蛋白配体-1(PSGL-1)。采用放免法分析(radioimmunoassay)测定血浆肾素活性(PRA)、血浆中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、胰岛素(Ins)、C-肽(C-P)含量。使用循环酶法检测血浆同型半胱氨酸浓度。
结果：22名健康志愿者中,一人因不能耐受高盐饮食退出研究,一人因在高盐期出现频发室性早搏,研究者认为不能继续实验。其余20名志愿者完成全部饮食干预及血液和尿液的有关检测,并根据24小时尿量、尿钠总量、尿肌酐总量以及血钠水平等指标进行质量控制并判定所得实验数据可靠。
(1)血压、心率的变化：收缩压(systolic blood pressure, SBP)、舒张压(diastolic blood pressure, DBP)在基线水平、高盐饮食第一天、高盐饮食第七天、低盐饮食第一天和低盐饮食第七天无显著性变化(P=0.6677和P=0.4915)。而心率在这五个时间点比较有统计学差异(P=0.0007),其中高盐饮食第一天、第七天较基线水平显著性增快(P<0.05),而低盐饮食时回落至基线水平(P>0.05)。
(2)血糖代谢相关变化：与基线水平比较,血浆胰岛素水平、胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(QUICKI)在高盐和低盐饮食后均无明显变化(P分别等于0.0655,0.2529,0.5057)。而C-肽水平和胰岛β细胞功能指数(HOMA-β)在基线、高盐和低盐饮食后均有统计学差异(P<0.0001；P=0.0008)。其中高盐饮食末较基线水平显著降低(P<0.05),低盐饮食末回升,并且HOMA-β升高有统计学意义(P<0.05)。
(3) RAAS系统相关变化：与基线水平比较,血浆肾素活性和AngⅡ水平在高盐和低盐饮食后均无明显变化(P=0.5315和P=0.1100)。血浆ALD水平在三个时间点比较有显著性变化(P=0.0436),其中高盐饮食末较基线水平显著性降低(P<0.05)；低盐饮食7d回升至基线水平。
(4)单核细胞亚群变化：外周血单核细胞总数和CD14++CD16型单核细胞(经典型单核细胞,Monl)在低盐饮食第一天轻度增加,其余各时间点无明显变化(P总数=0.0199,PMon1数量=0.0264)。CD14+CD16++型单核细胞(非经典型单核细胞,Mon3)数量和比例在低盐饮食第七天略有增加(P<0.05),其余各时间点无明显变化(P分别为0.0002,0.0122)。
CD14++CD16+型单核细胞(中间型单核细胞,Mon2)数量和比例在高盐饮食第一天明显增加,并持续增多至低盐饮食第一天(P均<0.0001),其中高盐饮食第一天与其他各时间点比较均有统计学差异(P均<0.0001)。
(5)MPA的形成变化：MPA数量在高盐饮食第一天显著增多并伴有比例升高,持续增多至低盐饮食第一天(P均<0.0001),分别与基线、低盐饮食第七天比较均有统计学差异(P均<0.05)；CD14++CD16+型单核细胞形成MPA比例在高盐饮食第一天和低盐饮食第一天显著升高,并有统计学差异(P=0.0002)。
CD14++CD16+型单核细胞形成MPA的比例在高盐饮食第一天显著增多,高盐饮食第七天达到顶峰,一直持续到低盐饮食第一天(P<0.0001)。其中高盐饮食第一天、第七天与其他各时间点比较均有统计学差异(P均<0.05)。而低盐饮食第七天较基线显著性降低(P<0.001)。不仅如此CD14++CD16+型单核细胞在5个时间点形成MPA的比例均较其他2型单核细胞高,分别占(32.53±6.68)%,(47.92±14.89)%,(55.12±12.08)%,(64.09±17.88)%,(19.15±7.89)%。CD14+CD16++型单核细胞在五个时间点形成MPA的比例无明显变化(P=0.2254)。
(6)单核细胞相关基因变化：MCP-1、CCL5、NF-κB、TGF-β和CX3CR1等基因mRNA表达水平在高盐饮食末分别升高至基线的1.16倍、2.22倍、1.15倍、1.06倍和1.03倍。低盐饮食末均回落至基线水平。其中CCL5、NF-κB升高有统计学意义(P<0.05)。Arg-1基因mRNA的表达水平在高盐饮食末降低至基线的0.64倍。低盐饮食末升高至基线的1.22倍,与高盐饮食末比较也显著升高(P=0.0403)。PSGL-1在高盐饮食末的表达水平与基线水平比较无统计学意义(P=0.0553),而低盐饮食末的水平较基线、高盐饮食末显著性降低(P<0.0001和P=0.0262)。
结论：本研究首次证实高盐饮食能够引起人循环中CD14++CD16+型单核细胞及单核细胞与血小板聚集体数量的增加,并伴有单核细胞炎性相关基因表达的上调,同时上述效应可被低盐饮食所逆转。本研究提出了基于单核细胞亚群失衡的高盐摄入靶器官损伤新机制,为相关疾病的防治提供了新的理论基础和人群研究证据。
Objective:High salt diet (HS) is not only the contributor to hypertension, but also can induce target organ damage (TOD) independent of blood pressure level. Monocyte is one of the main players in inflammatory response which is critical for the initiation and development of TOD. Recent evidence indicates that human circulating monocytes are at least composed of three subsets with distinct physiological functions, including classical (CD14++CD16",[Mon1]), intermediate (CD14++CD16+,[Mon2]), and non-classical (CD14+CD16++,[Mon3]) monocytes. Among them, CD14++CD16++monocytes were considered as "pro-inflammatory" monocytes, participating in a variety of inflammatory diseases, especially in the development of atherosclerosis. Moreover, the formation of monocyte-platelet aggregates (MPA), an sensitive marker for in vivo platelet activation, would further facilitate monocyte adhension to endothelial cells, and consequently, migration to subendotheial region. However, it remains unclear whether HS could have an impact on monocyte subsets phenotype and MPA formation, and thus contributes to the exacerbation of TOD. Therefore, the purpose of present study is to investigate the dynamics of phenotype change in human circulating monocyte subsets induced by high and low dietary salt intake, and exploring their potential mechanisms.
Methods:A total of22healthy volunteers were recruited in our dietary intervention trial (10male aged30.10±2.99years old and12female aged29.40±2.65years old). The participants were provided with HS (15g NaCl per day) for7d and LS (5g NaCl per day) for7d. All foods and beverages were prepared by study dietitians and provided by the study staff.24-h urine was collected at baseline,24h after HS,7d after HS,3d after LS and7d after LS. Overnight fasting blood samples were drawn at baseline,24h after HS,7d after HS,24h after LS and7d after LS. Monocyte subsets and their association with platelet aggregates were analyzed using a four-color flow cytometric platform, based on CD86, CD14, CD16and CD41. Circulating monocytes from each participant were further purified by density-gradient centrifugation to harvest peripheral blood mononuclear cells (PBMC), followed by magnetic activated cell sorting (MACS) by positive selection using anti-human CD14coated microbeads at baseline,7d after HS and7d after LS. Total RNA of purified monocytes was extracted using standard TRIzol procedure. Real-time PCR was used to analyze the mRNA expression of related pro-inflammatory and anti-inflammatory molecules, including C-C chemokine ligand5(CCL5), C-C chemokine receptor5(CCR5), monocyte chemotactic protein-1(MCP-1), C-C chemokine receptor2(CCR2), transforming growth factor-β (TGF-β), tumor necrosis factor-a (TNF-a), nuclear factor-KB (NF-κB), C-X3-C chemokine receptor1(CX3CR1), arginase-1(Arg-1) and P-selectin glycoprotein ligand-1(PSGL-1). Radioimmunoassay was used to detect plasma level of plasma renin activity (PRA), AngiotensinⅡ (Ang Ⅱ), aldosterone (ALD), Insulin (Ins) and C-Peptide (C-P). Enzymatic cycling assay was used to detect serum level of homocysteine (Hey).
Results:Of the22healthy volunteers,20subjects completed the dietary intervention and related blood and urine sampling.2subjects withdrew either because of intolerance to HS diets, or due to increased ventricular premature beats during HS intervention. The results from the24-h urinary excretions of sodium and creatinine showed excellent compliance with the study diets. During intervention, there were no significant changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at any time points (SBP P for trend:0.6677and DBP P for trend:0.4915). Heart rate increased significantly after HS compared with baseline (P<0.05), and regressed to baseline level after LS. Plasma level of Ins, HOMA-IR and QUICKI did not changed by HS and LS intervention significantly(P for trend:0.0655,0.2529,0.5057). C-P and HOMA-P decreased dramatically after HS compared with baseline, and returned after LS (P for trend <0.0001, P for trend0.0008). In addition, plasma PRA and Angll did not change significantly between baseline, HS and LS (P for trend:0.5315,0.1100). Whereas plasma ALD were significantly inhibited by HS and returned to baseline levels after LS (P for trend:0.0436). Total monocyte count and CD14++CD16-monocytes [classical, Monl] showed mild increase at LS24h (P for trend:0.0199,0.0264, respectively). CD14+CD16++monocyte count and percent [non-classical Mon3] increased slightly at LS7d (P for trend:0.0002,0.0122). There was a dramatic increase of CD14++CD16+monocyte count and percent [intermediate, Mon2] one day after HS, and this trend persisted till one day after LS (P for trend:<0.0001), the magnitude of which exhibited statistical significance compared with those of other time-points (P for trend:<0.0001). MPA count and percent in periphery blood increased significantly at HS24h, and lasted until LS24h (P for trend:<0.0001). This trend could be completely normalized after7days of LS diets. MPA in association with Mon2exhibited coordinated change with Mon2(P for trend:<0.0001). Moreover. Mon2subset had the highest binding affinity with platelet compared with other subsets at any time points (32.53±6.68)%,(47.92±14.89)%,(55.12±12.08)%,(64.09±17.88)%,(19.15±7.89)%for serial five time points, respectively. The mRNA expression level of inflammatory cytokines including MCP-1, CCL5, NF-κB, TGF-β and CX3CR1increased after HS7d, and returned to baseline after LS. The mRNA expression of CCL5and NF-κB at HS7d had statistical significance compared with baseline (P<0.05). The expression of Ang-1decreased after HS7d and increased significantly after LS7d (P<0.05). The mRNA expression of PSGL-1at HS7d mildly decreased (P for trend:0.0553). In comparison with baseline and HS7d, the expression of PSGL-1at LS7d decreased significantly (P for trend0.0001, P for trend0.0262).
Conclusions:The present study, to the best of our knowledge, for the first time provides human evidence that variation in dietary salt intake could induce coordinated monocyte subsets dynamics and their association with MPA. Specifically, an increase in dietary salt could lead to a rapid and proportional expansion of CD14++CD16+pool, followed by a gradual decrease despite adherence to high salt diet, which could be normalized by low salt intake. In addition, there is a paralleled relationship between MPA dynamics and the change of CD14++CD16+monocytes in response to fluctuation in dietary salt intake. These evidence may have broad clinical implications for high dietary salt intake induced end organ injury, atherosclerotic lesion development, and acute thromboembolic risk.
研究内容与方法：共纳入健康志愿者22人。男性10人,平均30.10±2.99岁；女性12人,平均29.40±2.65岁。先后给予高盐饮食(15g/d)7天和低盐饮食(5g/d)7天。所有饮食均由研究组提供,并在同一地点进餐。在基线最后一天、高盐饮食第一天、高盐饮食第七天、低盐饮食第三天、低盐饮食第七天收集24小时尿。分别在基线最后一天,高盐饮食第二天、高盐饮食第七天、低盐饮食第二天,低盐饮食第七天采集受试者外周血进行单核细胞亚群和MPA的流式细胞术(flow cytometry, FCM)检测,对单核细胞表型和血小板标志分子CD14.CD16,CD86和CD41进行四色分析。对基线最后一天,高盐第七天和低盐第七天采集外周血使用密度梯度离心法分离外周血单个核细胞(peripheral blood mononuclear cell, PBMC),并采用磁性细胞分选技术(magnetic activated cell sorting, MACS)以CD14阳性分选免疫磁珠纯化单核细胞。使用TRIzol试剂裂解纯化后的单核细胞,提取总RNA;采用实时荧光定量聚合酶链反应(Real-TimePCR)对单核细胞炎症相关因子和炎症抑制因子的基因表达水平进行检测,包括：C-C趋化因子配体5(CCL5)、C-C趋化因子受体5(CCR5)、单核细胞趋化因子-1(MCP-1)、C-C趋化因子受体2(CCR2)、转化生长因子-β(TGF-β)、肿瘤坏死因子-α(TNF-α)、核因子-κB(NF-κB)、C-X3-C趋化因子受体1(CX3CR1).精氨酸酶-1(Arg-1)、P选择素糖蛋白配体-1(PSGL-1)。采用放免法分析(radioimmunoassay)测定血浆肾素活性(PRA)、血浆中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)、胰岛素(Ins)、C-肽(C-P)含量。使用循环酶法检测血浆同型半胱氨酸浓度。
结果：22名健康志愿者中,一人因不能耐受高盐饮食退出研究,一人因在高盐期出现频发室性早搏,研究者认为不能继续实验。其余20名志愿者完成全部饮食干预及血液和尿液的有关检测,并根据24小时尿量、尿钠总量、尿肌酐总量以及血钠水平等指标进行质量控制并判定所得实验数据可靠。
(1)血压、心率的变化：收缩压(systolic blood pressure, SBP)、舒张压(diastolic blood pressure, DBP)在基线水平、高盐饮食第一天、高盐饮食第七天、低盐饮食第一天和低盐饮食第七天无显著性变化(P=0.6677和P=0.4915)。而心率在这五个时间点比较有统计学差异(P=0.0007),其中高盐饮食第一天、第七天较基线水平显著性增快(P<0.05),而低盐饮食时回落至基线水平(P>0.05)。
(2)血糖代谢相关变化：与基线水平比较,血浆胰岛素水平、胰岛素抵抗指数(HOMA-IR)和胰岛素敏感指数(QUICKI)在高盐和低盐饮食后均无明显变化(P分别等于0.0655,0.2529,0.5057)。而C-肽水平和胰岛β细胞功能指数(HOMA-β)在基线、高盐和低盐饮食后均有统计学差异(P<0.0001；P=0.0008)。其中高盐饮食末较基线水平显著降低(P<0.05),低盐饮食末回升,并且HOMA-β升高有统计学意义(P<0.05)。
(3) RAAS系统相关变化：与基线水平比较,血浆肾素活性和AngⅡ水平在高盐和低盐饮食后均无明显变化(P=0.5315和P=0.1100)。血浆ALD水平在三个时间点比较有显著性变化(P=0.0436),其中高盐饮食末较基线水平显著性降低(P<0.05)；低盐饮食7d回升至基线水平。
(4)单核细胞亚群变化：外周血单核细胞总数和CD14++CD16型单核细胞(经典型单核细胞,Monl)在低盐饮食第一天轻度增加,其余各时间点无明显变化(P总数=0.0199,PMon1数量=0.0264)。CD14+CD16++型单核细胞(非经典型单核细胞,Mon3)数量和比例在低盐饮食第七天略有增加(P<0.05),其余各时间点无明显变化(P分别为0.0002,0.0122)。
CD14++CD16+型单核细胞(中间型单核细胞,Mon2)数量和比例在高盐饮食第一天明显增加,并持续增多至低盐饮食第一天(P均<0.0001),其中高盐饮食第一天与其他各时间点比较均有统计学差异(P均<0.0001)。
(5)MPA的形成变化：MPA数量在高盐饮食第一天显著增多并伴有比例升高,持续增多至低盐饮食第一天(P均<0.0001),分别与基线、低盐饮食第七天比较均有统计学差异(P均<0.05)；CD14++CD16+型单核细胞形成MPA比例在高盐饮食第一天和低盐饮食第一天显著升高,并有统计学差异(P=0.0002)。
CD14++CD16+型单核细胞形成MPA的比例在高盐饮食第一天显著增多,高盐饮食第七天达到顶峰,一直持续到低盐饮食第一天(P<0.0001)。其中高盐饮食第一天、第七天与其他各时间点比较均有统计学差异(P均<0.05)。而低盐饮食第七天较基线显著性降低(P<0.001)。不仅如此CD14++CD16+型单核细胞在5个时间点形成MPA的比例均较其他2型单核细胞高,分别占(32.53±6.68)%,(47.92±14.89)%,(55.12±12.08)%,(64.09±17.88)%,(19.15±7.89)%。CD14+CD16++型单核细胞在五个时间点形成MPA的比例无明显变化(P=0.2254)。
(6)单核细胞相关基因变化：MCP-1、CCL5、NF-κB、TGF-β和CX3CR1等基因mRNA表达水平在高盐饮食末分别升高至基线的1.16倍、2.22倍、1.15倍、1.06倍和1.03倍。低盐饮食末均回落至基线水平。其中CCL5、NF-κB升高有统计学意义(P<0.05)。Arg-1基因mRNA的表达水平在高盐饮食末降低至基线的0.64倍。低盐饮食末升高至基线的1.22倍,与高盐饮食末比较也显著升高(P=0.0403)。PSGL-1在高盐饮食末的表达水平与基线水平比较无统计学意义(P=0.0553),而低盐饮食末的水平较基线、高盐饮食末显著性降低(P<0.0001和P=0.0262)。
结论：本研究首次证实高盐饮食能够引起人循环中CD14++CD16+型单核细胞及单核细胞与血小板聚集体数量的增加,并伴有单核细胞炎性相关基因表达的上调,同时上述效应可被低盐饮食所逆转。本研究提出了基于单核细胞亚群失衡的高盐摄入靶器官损伤新机制,为相关疾病的防治提供了新的理论基础和人群研究证据。
Objective:High salt diet (HS) is not only the contributor to hypertension, but also can induce target organ damage (TOD) independent of blood pressure level. Monocyte is one of the main players in inflammatory response which is critical for the initiation and development of TOD. Recent evidence indicates that human circulating monocytes are at least composed of three subsets with distinct physiological functions, including classical (CD14++CD16",[Mon1]), intermediate (CD14++CD16+,[Mon2]), and non-classical (CD14+CD16++,[Mon3]) monocytes. Among them, CD14++CD16++monocytes were considered as "pro-inflammatory" monocytes, participating in a variety of inflammatory diseases, especially in the development of atherosclerosis. Moreover, the formation of monocyte-platelet aggregates (MPA), an sensitive marker for in vivo platelet activation, would further facilitate monocyte adhension to endothelial cells, and consequently, migration to subendotheial region. However, it remains unclear whether HS could have an impact on monocyte subsets phenotype and MPA formation, and thus contributes to the exacerbation of TOD. Therefore, the purpose of present study is to investigate the dynamics of phenotype change in human circulating monocyte subsets induced by high and low dietary salt intake, and exploring their potential mechanisms.
Methods:A total of22healthy volunteers were recruited in our dietary intervention trial (10male aged30.10±2.99years old and12female aged29.40±2.65years old). The participants were provided with HS (15g NaCl per day) for7d and LS (5g NaCl per day) for7d. All foods and beverages were prepared by study dietitians and provided by the study staff.24-h urine was collected at baseline,24h after HS,7d after HS,3d after LS and7d after LS. Overnight fasting blood samples were drawn at baseline,24h after HS,7d after HS,24h after LS and7d after LS. Monocyte subsets and their association with platelet aggregates were analyzed using a four-color flow cytometric platform, based on CD86, CD14, CD16and CD41. Circulating monocytes from each participant were further purified by density-gradient centrifugation to harvest peripheral blood mononuclear cells (PBMC), followed by magnetic activated cell sorting (MACS) by positive selection using anti-human CD14coated microbeads at baseline,7d after HS and7d after LS. Total RNA of purified monocytes was extracted using standard TRIzol procedure. Real-time PCR was used to analyze the mRNA expression of related pro-inflammatory and anti-inflammatory molecules, including C-C chemokine ligand5(CCL5), C-C chemokine receptor5(CCR5), monocyte chemotactic protein-1(MCP-1), C-C chemokine receptor2(CCR2), transforming growth factor-β (TGF-β), tumor necrosis factor-a (TNF-a), nuclear factor-KB (NF-κB), C-X3-C chemokine receptor1(CX3CR1), arginase-1(Arg-1) and P-selectin glycoprotein ligand-1(PSGL-1). Radioimmunoassay was used to detect plasma level of plasma renin activity (PRA), AngiotensinⅡ (Ang Ⅱ), aldosterone (ALD), Insulin (Ins) and C-Peptide (C-P). Enzymatic cycling assay was used to detect serum level of homocysteine (Hey).
Results:Of the22healthy volunteers,20subjects completed the dietary intervention and related blood and urine sampling.2subjects withdrew either because of intolerance to HS diets, or due to increased ventricular premature beats during HS intervention. The results from the24-h urinary excretions of sodium and creatinine showed excellent compliance with the study diets. During intervention, there were no significant changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) at any time points (SBP P for trend:0.6677and DBP P for trend:0.4915). Heart rate increased significantly after HS compared with baseline (P<0.05), and regressed to baseline level after LS. Plasma level of Ins, HOMA-IR and QUICKI did not changed by HS and LS intervention significantly(P for trend:0.0655,0.2529,0.5057). C-P and HOMA-P decreased dramatically after HS compared with baseline, and returned after LS (P for trend <0.0001, P for trend0.0008). In addition, plasma PRA and Angll did not change significantly between baseline, HS and LS (P for trend:0.5315,0.1100). Whereas plasma ALD were significantly inhibited by HS and returned to baseline levels after LS (P for trend:0.0436). Total monocyte count and CD14++CD16-monocytes [classical, Monl] showed mild increase at LS24h (P for trend:0.0199,0.0264, respectively). CD14+CD16++monocyte count and percent [non-classical Mon3] increased slightly at LS7d (P for trend:0.0002,0.0122). There was a dramatic increase of CD14++CD16+monocyte count and percent [intermediate, Mon2] one day after HS, and this trend persisted till one day after LS (P for trend:<0.0001), the magnitude of which exhibited statistical significance compared with those of other time-points (P for trend:<0.0001). MPA count and percent in periphery blood increased significantly at HS24h, and lasted until LS24h (P for trend:<0.0001). This trend could be completely normalized after7days of LS diets. MPA in association with Mon2exhibited coordinated change with Mon2(P for trend:<0.0001). Moreover. Mon2subset had the highest binding affinity with platelet compared with other subsets at any time points (32.53±6.68)%,(47.92±14.89)%,(55.12±12.08)%,(64.09±17.88)%,(19.15±7.89)%for serial five time points, respectively. The mRNA expression level of inflammatory cytokines including MCP-1, CCL5, NF-κB, TGF-β and CX3CR1increased after HS7d, and returned to baseline after LS. The mRNA expression of CCL5and NF-κB at HS7d had statistical significance compared with baseline (P<0.05). The expression of Ang-1decreased after HS7d and increased significantly after LS7d (P<0.05). The mRNA expression of PSGL-1at HS7d mildly decreased (P for trend:0.0553). In comparison with baseline and HS7d, the expression of PSGL-1at LS7d decreased significantly (P for trend0.0001, P for trend0.0262).
Conclusions:The present study, to the best of our knowledge, for the first time provides human evidence that variation in dietary salt intake could induce coordinated monocyte subsets dynamics and their association with MPA. Specifically, an increase in dietary salt could lead to a rapid and proportional expansion of CD14++CD16+pool, followed by a gradual decrease despite adherence to high salt diet, which could be normalized by low salt intake. In addition, there is a paralleled relationship between MPA dynamics and the change of CD14++CD16+monocytes in response to fluctuation in dietary salt intake. These evidence may have broad clinical implications for high dietary salt intake induced end organ injury, atherosclerotic lesion development, and acute thromboembolic risk.
引文
[1]Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics--2012 update:a report from the American Heart Association[J]. Circulation,2012,125(1):e2-e220.
[2]Intersalt:an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and, potassium excretion. Intersalt Cooperative Research Group[J]. BMJ,1988,297(6644):319-28.
[3]Mimran A, du Cailar G. Dietary sodium:the dark horse amongst cardiovascular and renal risk factors[J]. Nephrol Dial Transplant,2008,23(7): 2138-41.
[4]Gao F, Han ZQ, Zhou X, et al. High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats:time window of left ventricular functional transition and its relation to salt-loading doses[J]. Clin Exp Hypertens,2011, 33(7):492-9.
[5]Lin L, Phillips WE, Manning RD. Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension[J]. J Am Soc Hypertens,2009,3(5):306-14.
[6]Boesen El, Williams DL, Pollock JS, et al. Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats[J]. Clin Exp Pharmacol Physiol,2010,37(10):1016-22.
[7]Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+CD16+ monocytes in obesity and during weight loss:relationships with fat mass and subclinical atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2011,31(10): 2322-30.
[8]Tapp LD, Shantsila E, Wrigley BJ, et al. The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction[J]. J Thromb Haemost,2011,
[9]Tsujioka H, Imanishi T, Ikejima H, et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction[J]. J Am Coll Cardiol,2009,54(2):130-8.
[10]Mantovani A, Garlanda C, Locati M. Macrophage diversity and polarization in atherosclerosis:a question of balance[J]. Arterioscler Thromb Vasc Biol,2009,29(10):1419-23.
[11]Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions[J]. J Exp Med,2007,204(12):3037-47.
[12]Furman MI, Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction[J]. J Am Coll Cardiol,2001,38(4):1002-6.
[13]Kuckleburg CJ, Yates CM, Kalia N, et al. Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation[J]. Cardiovasc Res,2011,91(1):134-41.
[14]Simon DI, Ezratty AM, Francis SA, et al. Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18):a nonplasmin fibrinolytic pathway[J]. Blood,1993,82(8):2414-22.
[15]van Gils JM, da Costa Martins PA, Mol A, et al. Transendothelial migration drives dissociation of plateletmonocyte complexes[J]. Thromb Haemost,2008, 100(2):271-9.
[16]Auffray C, Sieweke MH, Geissmann F. Blood monocytes:development, heterogeneity, and relationship with dendritic cells[J]. Annu Rev Immunol,2009,27(669-92.
[17]Woollard KJ, Geissmann F. Monocytes in atherosclerosis:subsets and functions[J]. Nat Rev Cardiol,2010,7(2):77-86.
[18]Geissmann F, Gordon S, Hume DA, et al. Unravelling mononuclear phagocyte heterogeneity[J]. Nat Rev Immunol,2010,10(453-460.
[19]Wong KL, Yeap WH, Tai JJ, et al. The three human monocyte subsets: implications for health and disease[J]. Immunol Res,2012,
[20]Hristov M, Leyendecker T, Schuhmann C, et al. Circulating monocyte subsets and cardiovascular risk factors in coronary artery disease[J]. Thromb Haemost,2010,104(2):412-4.
[21]Kashiwagi M, Imanishi T, Tsujioka H, et al. Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris[J]. Atherosclerosis,2010,212(1):171-6.
[22]Heine GH, Ulrich C, Seibert E, et al. CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients[J]. Kidney Int,2008,73(5):622-9.
[23]Rogacev KS, Ziegelin M, Ulrich C, et al. Haemodialysis-induced transient CD 16+ monocytopenia and cardiovascular outcome[J]. Nephrol Dial Transplant,2009,24(11):3480-6.
[24]Keating FK, Dauerman HL, Whitaker DA, et al. Increased expression of platelet P-selectin and formation of platelet-leukocyte aggregates in blood from patients treated with unfractionated heparin plus eptifibatide compared with bivalirudin[J]. Thromb Res,2006,118(3):361-9.
[25]Wang J, Zhang S, Jin Y, et al. Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome[J]. International Journal of Cardiology,2007,115(361-365.
[26]Michelson AD. Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin:studies in baboons, human coronary intervention, and human acute myocardial infarction[J]. Circulation,2001,104(13):1533-7.
[27]Gremmela T, Koppa C, Seidingera D, et al. The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists-inducible platelet reactivity[J]. Atherosclerosis,2009,207(608-613.
[28]WHO. Reading Salt intake in population[A]. in report of a WHO Forum and Technical Meeting 5-7 October,2006 Paris, France. Switzerland:World Health Orgnization,2007:1-65.
[29]Zhou X, Liu JX. Shi R, et al. Compound ion salt, a novel low-sodium salt substitute:from animal study to community-based population trial [J]. Am J Hypertens,2009,22(9):934-42.
[30]Rogacev KS, Seiler S, Zawada AM, et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease[J]. Eur Heart J,2011,32(1):84-92.
[31]Gu D, Kelly TN, Hixson JE, et al. Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure [J]. J Hypertens,2010,28(6):1210-20.
[32]Hall JE, Mizelle HL, Hildebrandt DA, et al. Abnormal pressure natriuresis. A cause or a consequence of hypertension?[J]. Hypertension,1990,15(6 Pt 1): 547-59.
[33]de Wardener HE, MacGregor GA. The natriuretic hormone and essential hypertension [J]. Lancet,1982,1(8287):1450-4.
[34]Orlov SN, Mongin AA. Salt-sensing mechanisms in blood pressure regulation and hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(4): H2039-53.
[35]Sacks FM, Obarzanek E, Windhauser MM, et al. Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure[J]. Ann Epidemiol,1995,5(2):108-18.
[36]Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group[J]. N Engl J Med,2001,344(1):3-10.
[37]Weinberger MH, Fineberg NS, Fineberg SE, et al. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans[J]. Hypertension,2001, 37(2 Part 2):429-32.
[38]Blaustein MP, Leenen FH, Chen L, et al. How NaCl raises blood pressure:a new paradigm for the pathogenesis of salt-dependent hypertension[J]. Am J Physiol Heart Circ Physiol,2012,302(5):H1031-49.
[39]Sakai RR, McEwen BS, Fluharty SJ, et al. The amygdala:site of genomic and nongenomic arousal of aldosterone-induced sodium intake[J]. Kidney Int,2000,57(4):1337-45.
[40]Davern PJ, Nguyen-Huu TP, La Greca L, et al. Role of the sympathetic nervous system in Schlager genetically hypertensive mice[J]. Hypertension,2009,54(4):852-9.
[41]Santos RA, Ferreira AJ, Simoes ESAC. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis[J]. Exp Physiol,2008,93(5):519-27.
[42]Oudit GY, Herzenberg AM, Kassiri Z, et al. Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin Ⅱ-dependent glomerulosclerosis[J]. Am J Pathol,2006,168(6):1808-20.
[43]Hernandez Prada JA, Ferreira AJ, Katovich MJ, et al. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents[J]. Hypertension,2008,51(5):1312-7.
[44]Liu CX, Hu Q, Wang Y, et al. Angiotensin-converting enzyme (ACE) 2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy:a comparison with ACE inhibition[J]. Mol Med,2011,17(1-2): 59-69.
[45]Huang BS, White RA, Bi L, et al. Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake[J]. Am J Physiol Regul Integr Comp Physiol,2012,302(7): R825-32.
[46]Davern PJ, Head GA. Fos-related antigen immunoreactivity after acute and chronic angiotensin Ⅱ-induced hypertension in the rabbit brain[J]. Hypertension,2007,49(5):1170-7.
[47]刘治全,牟建军,李玉明.盐敏感性高血压[M].北京：人民卫生出版社,2011：166-170.
[48]Agarwal MK, Mirshahi F, Mirshahi M, et al. Immunochemical detection of the mineralocorticoid receptor in rat brain[J]. Neuroendocrinology.1993,58(5): 575-80.
[49]Franco M, Martinez F, Rodriguez-Iturbe B, et al. Angiotensin Ⅱ, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension[J]. Am J Physiol Renal Physiol,2006,291(6):F1281-7.
[50]Kobori H, Prieto-Carrasquero MC, Ozawa Y, et al. AT1 receptor mediated augmentation of intrarenal angiotensinogen in angiotensin Ⅱ-dependent hypertension[J]. Hypertension,2004,43(5):1126-32.
[51]Nishiyama A, Yoshizumi M, Rahman M, et al. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats[J]. Kidney Int,2004,65(3):972-81.
[52]Hayakawa H, Coffee K, Raij L. Endothelial dv.sfunction and cardiorenal injury in experimental salt-sensitive hypertension:effects of antihypertensive therapy [J]. Circulation,1997,96(7):2407-13.
[53]Kodama K, Adachi H, Sonoda J. Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension[J]. J Pharmacol Exp Ther,1997,283(2):625-9.
[54]Zhou MS, Adam AG, Jaimes EA, et al. In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin Ⅱ[J]. Hypertension,2003,42(5):945-51.
[55]Jaimes EA. Zhou MS, Pearse DD, et al. Upregulation of cortical COX-2 in salt-sensitive hypertension:role of angiotensin Ⅱ and reactive oxygen species[J]. Am J Physiol Renal Physiol,2008,294(2):F385-92.
[56]Banes-Berceli AK, Al-Azawi H, Proctor D, et al. Angiotensin Ⅱ utilizes Janus kinase 2 in hypertension, but not in the physiological control of blood pressure, during low-salt intake[J]. Am J Physiol Regul Integr Comp Physiol,2011, 301(4):R1169-76.
[57]Bernardi S, Toffoli B, Zennaro C, et al. High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage[J]. Nephrol Dial Transplant,2011,
[58]Bader M. Tissue renin-angiotensin-aldosterone systems:Targets for pharmacological therapy[J]. Annu Rev Pharmacol Toxicol,2010,50(439-65.
[59]Hoogwerf BJ. Renin-angiotensin system blockade and cardiovascular and renal protection [J]. Am J Cardiol,2010,105(1 Suppl):30A-5A.
[60]Nakamura T, Kataoka K, Tokutomi Y, et al. Novel mechanism of salt-induced glomerular injury:critical role of eNOS and angiotensin II[J]. J Hypertens,2011,29(8):1528-35.
[61]Chandramohan G, Bai Y, Norris K, et al. Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-kappaB activity in salt-sensitive and -resistant rat kidneys[J]. Am J Nephrol,2008,28(1):158-67.
[62]Otsuka F, Yamauchi T, Kataoka H, et al. Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in dahl salt-sensitive rats[J]. Am J Physiol,1998,274(6 Pt 2):R1797-806.
[63]Varagic J, Ahmad S, Brosnihan KB, et al. Salt-induced renal injury in spontaneously hypertensive rats:effects of nebivolol[J]. Am J Nephrol,2010, 32(6):557-66.
[64]Funder JW, Mihailidou AS. Aldosterone and mineralocorticoid receptors: Clinical studies and basic biology[J]. Mol Cell Endocrinol,2009,301(1-2): 2-6.
[65]Schiffrin EL. Effects of aldosterone on the vasculature[J]. Hypertension,2006, 47(3):312-8.
[66]Bunda S, Liu P, Wang Y, et al. Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-Ⅰ receptors in a mineralocorticoid receptor-independent manner[J]. Am J Pathol,2007, 171(3):809-19.
[67]Kawarazaki H, Ando K, Fujita M, et al. Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats[J]. Am J Physiol Renal Physiol,2011,300(6):F1402-9.
[68]Shibata S, Nagase M, Yoshida S, et al. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1[J]. Hypertension,2007,49(2):355-64.
[69]Pitt B. Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction[J]. N Engl J Med,2003,348(14):1309-21.
[70]Lastra G. Whaley-Connell A, Manrique C, et al. Low-dose spironolactone reduces reactive oxygen species generation and improves insulin-stimulated glucose transport in skeletal muscle in the TG(mRen2)27 rat[J]. Am J Physiol Endocrinol Metab,2008,295(1):E110-6.
[71]Wang H, Shimosawa T, Matsui H, et al. Paradoxical mineralocorticoid receptor activation and left ventricular diastolic dysfunction under high oxidative stress conditions[J]. J Hypertens,2008,26(7):1453-62.
[72]Griendling KK, Minieri CA, Ollerenshaw JD, et al. Angiotensin Ⅱ stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells[J]. Circ Res,1994,74(6):1141-8.
[73]du Cailar G, Fesler P, Ribstein J, et al. Dietary sodium, aldosterone, and left ventricular mass changes during long-term inhibition of the renin-angiotensin system[J]. Hypertension,2010,56(5):865-70.
[74]Falkner B, Hulman S, Kushner H. Hyperinsulinemia and blood pressure sensitivity to sodium in young blacks[J]. J Am Soc Nephrol,1992,3(4):940-6.
[75]Sharma AM, Schorr U, Distler A. Insulin resistance in young salt-sensitive normotensive subjects[J]. Hypertension,1993,21(3):273-9.
[76]Weinberger MH. Salt sensitivity of blood pressure in humans[J]. Hypertension,1996,27(3 Pt 2):481-90.
[77]Chen J, Gu D, Huang J, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China:a dietary intervention study[J]. Lancet,2009,373(9666):829-35.
[78]Chen J. Sodium sensitivity of blood pressure in Chinese populations[J]. Curr Hypertens Rep,2010,12(2):127-34.
[79]Lastra G, Manrique C, McFarlane SI, et al. Cardiometabolic syndrome and chronic kidney disease[J]. Curr Diab Rep,2006,6(3):207-12.
[80]Saiki A, Ohira M, Endo K, et al. Circulating angiotensin Ⅱ is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus[J]. Metabolism,2009,58(5):708-13.
[81]Modan M, Halkin H, Almog S, et al. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance[J]. J Clin Invest,1985,75(3): 809-17.
[82]Zawada AM, Rogacev KS, Rotter B, et al. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset[J]. Blood,2011, 118(12):e50-61.
[83]Tian N, Moore RS, Phillips WE, et al. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension[J]. Am J Physiol Regul Integr Comp Physiol,2008,295(6):R1858-65.
[84]Ozawa Y, Kobori H, Suzaki Y, et al. Sustained renal interstitial macrophage infiltration following chronic angiotensin Ⅱ infusions[J]. Am J Physiol Renal Physiol,2007,292(1):F330-9.
[85]Mattson DL, James L, Berdan EA, et al. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat[J]. Hypertension,2006,48(1):149-56.
[86]Tian N, Gu JW, Jordan S, et al. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,292(2):H1018-25.
[87]Tian N, Rose RA, Jordan S, et al. N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension[J]. J Hypertens,2006,24(11):2263-70.
[88]Tian N, Moore RS, Braddy S, et al. Interactions between oxidative stress and inflammation in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(6):H3388-95.
[89]Tian N, Thrasher KD, Gundy PD, et al. Antioxidant treatment prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Hypertension,2005,45(5):934-9.
[90]Crowley SD, Frey CW, Gould SK, et al. Stimulation of lymphocyte responses by angiotensin Ⅱ promotes kidney injury in hypertension[J]. Am J Physiol Renal Physiol,2008,295(2):F515-24.
[91]Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis[J]. Nature,2011,473(7347):317-25.
[92]Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options[J]. Nat Med,2011,17(11):1410-22.
[93]Hansson GK. Inflammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352(16):1685-95.
[94]Hansson GK, Libby P. The immune response in atherosclerosis:a double-edged sword[J]. Nat Rev Immunol,2006,6(7):508-19.
[95]Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood[J]. Blood,1989,74(7):2527-34.
[96]Ziegler-Heitbrock L. The CD 14+ CD 16+ blood monocytes:their role in infection and inflammation[J]. J Leukoc Biol,2007,81(3):584-92.
[97]Schlitt A, Heine GH, Blankenberg S, et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels[J]. Thromb Haemost,2004,92(2):419-24.
[98]Ancuta P, Rao R, Moses A, et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes[J]. J Exp Med,2003,197(12):1701-7.
[99]Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets[J]. Immunobiology,2006,211(6-8):609-18.
[100]Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. Nomenclature of monocytes and dendritic cells in blood[J]. Blood,2010,116(16):e74-80.
[101]Heimbeck I, Hofer TP, Eder C, et al. Standardized single-platform assay for human monocyte subpopulations:Lower CD14+CD16++ monocytes in females[J]. Cytometry A,2010,77(9):823-30.
[102]Wong KL, Tai JJ, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets[J]. Blood,2011,118(5):e16-31.
[103]Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris[J]. Circ J,2010,74(2):337-45.
[104]Berg KE, Ljungcrantz I, Andersson L, et al. Elevated CD14++CD16-monocytes predict cardiovascular events[J]. Circ Cardiovasc Genet,2012,5(1): 122-31.
[105]Csiszar A, Wang M, Lakatta EG, et al. Inflammation and endothelial dysfunction during aging:role of NF-kappaB[J]. J Appl Physiol,2008,105(4): 1333-41.
[106]Gu JW, Tian N, Shparago M, et al. Renal NF-kappaB activation and TNF-alpha upregulation correlate with salt-sensitive hypertension in Dahl salt-sensitive rats[J]. Am J Physiol Regul Integr Comp Physiol,2006,291(6): R1817-24.
[107]Rodriguez-Iturbe B, Ferrebuz A, Vanegas V, et al. Early and sustained inhibition of nuclear factor-kappaB prevents hypertension in spontaneously hypertensive rats[J]. J Pharmacol Exp Ther,2005,315(1):51-7.
[108]Elks CM, Mariappan N, Haque M, et al. Chronic NF-{kappa}B blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR[J]. Am J Physiol Renal Physiol,2009,296(2): F298-305.
[109]Sanz-Rosa D, Oubina MP, Cediel E, et al. Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR:role of NF-kappaB/IkappaB system[J]. Am J Physiol Heart Circ Physiol,2005,288(1): H111-5.
[110]Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis[J]. N Engl J Med,1994,331(19):1286-92.
[111]Yu HC, Burrell LM, Black MJ, et al. Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats[J]. Circulation,1998,98(23): 2621-8.
[112]Ying WZ, Aaron K, Wang PX, et al. Potassium inhibits dietary salt-induced transforming growth factor-beta production[J]. Hypertension,2009,54(5): 1159-63.
[113]Combadiere C, Potteaux S, Rodero M, et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice[J]. Circulation,2008,117(13):1649-57.
[114]Braunersreuther V, Zernecke A, Arnaud C, et al. Ccr5 but not Ccrl deficiency reduces development of diet-induced atherosclerosis in mice[J]. Arterioscler Thromb Vase Biol,2007,27(2):373-9.
[115]Gkaliagkousi E, Corrigall V, Becker S, et al. Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension[J]. Eur Heart J,2009,30(24):3048-54.
[116]Mickelson JK, Lakkis NM, Villarreal-Levy G, et al. Leukocyte activation with platelet adhesion after coronary angioplasty:a mechanism for recurrent disease?[J]. J Am Coll Cardiol,1996,28(2):345-53.
[117]Htun P, Fateh-Moghadam S, Tomandl B, et al. Course of platelet activation and platelet-leukocyte interaction in cerebrovascular ischemia[J]. Stroke.2006, 37(9):2283-7.
[118]Smout J, Dyker A, Cleanthis M, et al. Platelet function following acute cerebral ischemia[J]. Angiology,2009,60(3):362-9.
[119]Harding SA, Sommerfield AJ, Sarma J, et al. Increased CD40 ligand and platelet-monocyte aggregates in patients with type 1 diabetes mellitus[J]. Atherosclerosis,2004,176(2):321-5.
[120]Weyrich AS, McIntyre TM, McEver RP, et al. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation[J]. J Clin Invest,1995,95(5):2297-303.
[121]Weyrich AS, Elstad MR, McEver RP, et al. Activated platelets signal chemokine synthesis by human monocytes[J]. J Clin Invest,1996,97(6): 1525-34.
[122]Dixon DA, Tolley ND, Bemis-Standoli K, et al. Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling[J]. J Clin Invest,2006,116(10):2727-38.
[123]da Costa Martins PA, van Gils JM, Mol A, et al. Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of betal and beta2 integrins[J]. J Leukoc Biol,2006,79(3):499-507.
[124]Cermak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor[J]. Blood,1993,82(2): 513-20.
[125]van der Logt CP, Dirven RJ, Reitsma PH, et al. Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester[J]. Blood Coagul Fibrinolysis,1994,5(2): 211-20.
[126]Panes O, Matus V, Saez CG, et al. Human platelets synthesize and express functional tissue factor[J]. Blood,2007,109(12):5242-50.
[127]Scholz T, Temmler U, Krause S, et al. Transfer of tissue factor from platelets to monocytes:role of platelet-derived microvesicles and CD62P[J]. Thromb Haemost,2002,88(6):1033-8.
[128]Le Guyader A, Davis-Gorman G, Copeland JG, et al. A flow cytometric method for determining the binding of coagulation factor X to monocytes in whole human blood[J]. J Immunol Methods,2004,292(1-2):207-15.
[129]Kappelmayer J, Kunapuli SP, Wyshock EG, et al. Characterization of monocyte-associated factor V[J]. Thromb Haemost,1993,70(2):273-80.
[130]Satta N, Freyssinet JM, Toti F. The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide[J]. Br J Haematol,1997,96(3):534-42.
[131]Passacquale G, Vamadevan P, Pereira L, et al. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes[J]. PLoS One,2011,6(10):e25595.
[132]Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD:searching for the best risk marker by multivariate modeling[J]. J Am Soc Nephrol,2005, 16 Suppl 1(S83-8.
[133]Zhou MS, Schulman IH, Raij L. Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension:role of nuclear factor kappa B activation[J]. J Hypertens,2010,28(3):527-35.
[1]Auffray C, Sieweke MH, Geissmann F. Blood monocytes:development, heterogeneity, and relationship with dendritic cells[J]. Annu Rev Immunol,2009,27(669-92.
[2]Swirski FK, Nahrendorf M, Etzrodt M, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites[J]. Science,2009, 325(5940):612-6.
[3]Geissmann F, Auffray C, Palframan R, et al. Blood monocytes:distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses[J]. Immunol Cell Biol,2008,86(5):398-408.
[4]Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties[J]. Immunity,2003,19(1):71-82.
[5]Serbina NV, Jia T, Hohl TM, et al. Monocyte-mediated defense against microbial pathogens[J]. Annu Rev Immunol,2008,26(421-52.
[6]Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection[J]. J Leukoc Biol,2007,82(2):244-52.
[7]Grage-Griebenow E, Flad HD, Ernst M. Heterogeneity of human peripheral blood monocyte subsets[J]. J Leukoc Biol,2001,69(1):11-20.
[8]Banchereau J, Steinman RM. Dendritic cells and the control of immunity[J]. Nature,1998,392(6673):245-52.
[9]Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets[J]. Immunobiology,2006,211(6-8):609-18.
[10]Varol C, Yona S, Jung S. Origins and tissue-context-dependent fates of blood monocytes[J]. Immunol Cell Biol,2009,87(1):30-8.
[11]Luft FC, Mervaala E, Muller DN, et al. Hypertension-induced end-organ damage:A new transgenic approach to an old problem[J]. Hypertension,1999, 33(1 Pt 2):212-8.
[12]Bautista LE. Inflammation, endothelial dysfunction, and the risk of high blood pressure:epidemiologic and biological evidence[J]. J Hum Hypertens,2003, 17(4):223-30.
[13]Granger DN, Vowinkel T, Petnehazy T. Modulation of the inflammatory response in cardiovascular disease[J]. Hypertension,2004,43(5):924-31.
[14]Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris[J]. Circ J,2010,74(2):337-45.
[15]Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD:searching for the best risk marker by multivariate modeling[J]. J Am Soc Nephrol,2005, 16Suppl1(S83-8.
[16]Kim F, Pham M, Luttrell I, et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity[J]. Circ Res,2007, 100(11):1589-96.
[17]Boyle PJ. Diabetes mellitus and macrovascular disease:mechanisms and mediators[J]. Am J Med,2007,120(9 Suppl 2):S12-7.
[18]Svendsen UG. Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice[J]. Acta Pathol Microbiol Scand A,1976,84(6):523-8.
[19]Bataillard A, Freiche JC, Vincent M, et al. Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat[J]. Thymus,1986,8(6): 321-30.
[20]Bataillard A, Renaudin C, Sassard J. Silica attenuates hypertension in Lyon hypertensive rats[J]. J Hypertens,1995,13(12 Pt 2):1581-4.
[21]Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin Ⅱ induced hypertension and vascular dysfunction [J]. J Exp Med,2007,204(10):2449-60.
[22]Rodriguez-Iturbe B, Quiroz Y, Nava M, et al. Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats[J]. Am J Physiol Renal Physiol,2002,282(2):F191-201.
[23]Alvarez V, Quiroz Y, Nava M, et al. Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells[J]. Am J Physiol Renal Physiol,2002,283(5):F1132-41.
[24]Vanegas V, Ferrebuz A, Quiroz Y, et al. Hypertension in Page (cellophane-wrapped) kidney is due to interstitial nephritis[J]. Kidney Int,2005,68(3):1161-70.
[25]Stewart T, Jung FF, Manning J, et al. Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension[J]. Kidney Int,2005,68(5):2180-8.
[26]Mattson DL, James L, Berdan EA, et al. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat[J]. Hypertension,2006,48(1):149-56.
[27]Tian N, Gu JW, Jordan S, et al. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,292(2):H1018-25.
[28]Crowley SD, Frey CW, Gould SK, et al. Stimulation of lymphocyte responses by angiotensin Ⅱ promotes kidney injury in hypertension[J]. Am J Physiol Renal Physiol,2008,295(2):F515-24.
[29]Pechman KR, Basile DP, Lund H, et al. Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure[J]. Am J Physiol Regul Integr Comp Physiol,2008,294(4):R1234-9.
[30]Seaberg EC, Munoz A, Lu M, et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003[J]. AIDS,2005,19(9):953-60.
[31]Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis[J]. Nature,2011,473(7347):317-25.
[32]Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options[J]. Nat Med,2011,17(11):1410-22.
[33]Woollard KJ, Geissmann F. Monocytes in atherosclerosis:subsets and functions[J]. Nat Rev Cardiol,2010,7(2):77-86.
[34]Hansson GK. Inflammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352(16):1685-95.
[35]Hansson GK, Libby P. The immune response in atherosclerosis:a double-edged sword[J]. Nat Rev Immunol,2006,6(7):508-19.
[36]Shah PK. Molecular mechanisms of plaque instability[J]. Curr Opin Lipidol,2007,18(5):492-9.
[37]Johnson-Tidey RR, McGregor JL, Taylor PR, et al. Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1[J]. Am J Pathol,1994, 144(5):952-61.
[38]Woollard KJ. Chin-Dusting J. Therapeutic targeting of p-selectin in atherosclerosis[J]. Inflamm Allergy Drug Targets,2007,6(1):69-74.
[39]Johnson RC, Chapman SM, Dong ZM, et al. Absence of P-selectin delays fatty streak formation in mice[J]. J Clin Invest,1997,99(5):1037-43.
[40]Dong ZM, Chapman SM, Brown AA, et al. The combined role of P- and E-selectins in atherosclerosis [J]. J Clin Invest,1998,102(1):145-52.
[41]Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2007,27(11):2292-301.
[42]Nageh MF, Sandberg ET, Marotti KR, et al. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol,1997,17(8):1517-20.
[43]Cybulsky MI, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis[J]. J Clin Invest,2001,107(10):1255-62.
[44]Girard JP, Springer TA. High endothelial venules (HEVs):specialized endothelium for lymphocyte migration[J]. Immunol Today,1995,16(9): 449-57.
[45]Qu C, Edwards EW, Tacke F, et al. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes[J]. J Exp Med,2004,200(10):1231-41.
[46]Combadiere C, Potteaux S, Rodero M, et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice[J]. Circulation,2008,117(13):1649-57.
[47]Saederup N, Chan L, Lira SA, et al. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2-/- mice:evidence for independent chemokine functions in atherogenesis[J]. Circulation,2008,117(13):1642-8.
[48]Lesnik P, Haskell CA, Charo IF. Decreased atherosclerosis in CX3CR1-/-mice reveals a role for fractalkine in atherogenesis[J]. J Clin Invest,2003, 111(3):333-40.
[49]Smith JD, Trogan E, Ginsberg M, et al. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E[J]. Proc Natl Acad Sci U S A,1995,92(18):8264-8.
[50]Qiao JH, Tripathi J, Mishra NK, et al. Role of macrophage colony-stimulating factor in atherosclerosis:studies of osteopetrotic mice[J]. Am J Pathol,1997, 150(5):1687-99.
[51]Ulrich C, Heine GH, Garcia P, et al. Increased expression of monocytic angiotensin-converting enzyme in dialysis patients with cardiovascular disease[J]. Nephrol Dial Transplant,2006,21(6):1596-602.
[52]Llodra J, Angeli V, Liu J, et al. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques[J]. Proc Natl Acad Sci U S A,2004,101(32):11779-84.
[53]Feig JE, Quick JS, Fisher EA. The role of a murine transplantation model of atherosclerosis regression in drug discovery[J]. Curr Opin Investig Drugs,2009,10(3):232-8.
[54]Guyton AC, Coleman TG, Cowley AV, Jr., et al. Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension[J]. Am J Med,1972,52(5):584-94.
[55]Franco M, Martinez F, Quiroz Y, et al. Renal angiotensin Ⅱ concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension[J]. Am J Physiol Regul Integr Comp Physiol,2007,293(1):R251-6.
[56]Tian N, Moore RS, Phillips WE, et al. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension [J]. Am J Physiol Regul Integr Comp Physiol,2008,295(6):R1858-65.
[57]Ozawa Y, Kobori H, Suzaki Y, et al. Sustained renal interstitial macrophage infiltration following chronic angiotensin Ⅱ infusions[J]. Am J Physiol Renal Physiol,2007,292(1):F330-9.
[58]Tian N, Rose RA, Jordan S, et al. N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension[J]. J Hypertens,2006,24(11):2263-70.
[59]Tian N, Moore RS, Braddy S, et al. Interactions between oxidative stress and inflammation in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(6):H3388-95.
[60]Tian N, Thrasher KD, Gundy PD, et al. Antioxidant treatment prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Hypertension,2005,45(5):934-9.
[61]Allcock GH, Venema RC, Pollock DM. ETA receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats[J]. Am J Physiol,1998,275(1 Pt 2):R245-52.
[62]Hayakawa H, Coffee K, Raij L. Endothelial dysfunction and cardiorenal injury in experimental salt-sensitive hypertension:effects of antihypertensive therapy[J]. Circulation,1997,96(7):2407-13.
[63]Kodama K, Adachi H, Sonoda J. Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension[J]. J Pharmacol Exp Ther,1997,283(2):625-9.
[64]Chandramohan G, Bai Y, Norris K, et al. Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-kappaB activity in salt-sensitive and -resistant rat kidneys[J]. Am J Nephrol,2008,28(1):158-67.
[65]Kobori H, Nangaku M, Navar LG, et al. The intrarenal renin-angiotensin system:from physiology to the pathobiology of hypertension and kidney disease[J]. Pharmacol Rev,2007,59(3):251-87.
[66]Nishiyama A, Yoshizumi M, Rahman M, et al. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats [J]. Kidney Int,2004,65(3):972-81.
[67]Zhou MS, Adam AG, Jaimes EA, et al. In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin Ⅱ[J]. Hypertension,2003,42(5):945-51.
[68]Jaimes EA, Zhou MS, Pearse DD, et al. Upregulation of cortical COX-2 in salt-sensitive hypertension:role of angiotensin Ⅱ and reactive oxygen species[J]. Am J Physiol Renal Physiol,2008,294(2):F385-92.
[69]Lin L, Phillips WE, Manning RD. Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension[J]. J Am Soc Hypertens,2009,3(5):306-14.
[70]Franco M, Martinez F, Rodriguez-Iturbe B, et al. Angiotensin Ⅱ, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension[J]. Am J Physiol Renal Physiol,2006,291(6):F1281-7.
[71]Kobori H, Prieto-Carrasquero MC, Ozawa Y, et al. ATI receptor mediated augmentation of intrarenal angiotensinogen in angiotensin Ⅱ-dependent hypertension[J]. Hypertension,2004,43(5):1126-32.
[72]Prieto-Carrasquero MC, Kobori H, Ozawa Y, et al. ATI receptor-mediated enhancement of collecting duct renin in angiotensin Ⅱ-dependent hypertensive rats[J]. Am J Physiol Renal Physiol,2005,289(3):F632-7.
[73]Otsuka F, Yamauchi T, Kataoka H, et al. Effects of chronic inhibition of ACE and ATI receptors on glomerular injury in dahl salt-sensitive rats[J]. Am J Physiol,1998,274(6 Pt 2):R1797-806.
[74]Machnik A, Neuhofer W, Jantsch J, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism[J]. Nat Med,2009,15(5):545-52.
[75]Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system[J]. Circulation,1991,83(6): 1849-65.
[76]Blasi ER, Rocha R, Rudolph AE, et al. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats[J]. Kidney Int,2003,63(5): 1791-800.
[77]Rocha R, Chander PN, Khanna K, et al. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats[J]. Hypertension,1998,31(1 Pt 2):451-8.
[78]Kretzler M, Koeppen-Hagemann I, Kriz W. Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat[J]. Virchows Arch,1994,425(2):181-93.
[79]Armanini D, Endres S, Kuhnle U, et al. Parallel determination of mineralocorticoid and glucocorticoid receptors in T-and B-lymphocytes of human spleen[J]. Acta Endocrinol (Copenh),1988,118(4):479-82.
[80]Armanini D, Strasser T, Weber PC. Binding of agonists and antagonists to mineralocorticoid receptors in human peripheral mononuclear leucocytes[J]. J Hypertens Suppl,1985,3(3):S157-9.
[81]Rickard AJ, Morgan J, Tesch G, et al. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure[J]. Hypertension,2009,54(3):537-43.
[82]Herrada AA, Contreras FJ, Marini NP, et al. Aldosterone promotes autoimmune damage by enhancing Thl7-mediated immunity [J]. J Immunol,2010,184(1):191-202.
[83]Miura R, Nakamura K, Miura D, et al. Aldosterone synthesis and cytokine production in human peripheral blood mononuclear cells[J]. J Pharmacol Sci,2006,102(3):288-95.
[84]Keidar S, Kaplan M, Pavlotzky E, et al. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development:a possible role for angiotensin-converting enzyme and the receptors for angiotensin Ⅱ and aldosterone[J]. Circulation.2004,109(18): 2213-20.
[85]Massy ZA, Guijarro C. Statins:effects beyond cholesterol lowering[J]. Nephrol Dial Transplant,2001,16(9):1738-41.
[86]Hartner A, Klanke B, Cordasic N, et al. Statin treatment reduces glomerular inflammation and podocyte damage in rat deoxycorticosterone-acetate-salt hypertension[J]. J Hypertens,2009,27(2):376-85.
[87]Blanco S, Vaquero M, Gomez-Guerrero C, et al. Potential role of angiotensin-converting enzyme inhibitors and statins on early podocyte damage in a model of type 2 diabetes mellitus, obesity, and mild hypertension[J]. Am J Hypertens,2005,18(4 Pt 1):557-65.
[88]Whaley-Connell A, DeMarco VG, Lastra G, et al. Insulin resistance, oxidative stress, and podocyte injury:role of rosuvastatin modulation of filtration barrier injury[J]. Am J Nephrol,2008,28(1):67-75.
[89]Ramirez R, Carracedo J, Soriano S, et al. Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis[J]. Am J Kidney Dis,2005,45(2):353-9.
[90]Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection):a randomised placebo-controlled trial[J]. Lancet,2011,377(9784):2181-92.
[91]Heine GH, Ortiz A, Massy ZA, et al. Monocyte subpopulations and cardiovascular risk in chronic kidney disease[J]. Nat Rev Nephrol,2012,
[92]Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome[J]. J Am Coll Cardiol.2008,52(19):1527-39.
[93]Auffray C, Fogg D, Garfa M, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior[J]. Science,2007, 317(5838):666-70.
[94]Yasaka T, Mantich NM, Boxer LA, et al. Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets[J]. J Immunol,1981, 127(4):1515-8.
[95]Weiner RS, Mason RR. Subfractionation of human blood monocyte subsets with Percoll[J]. Exp Hematol,1984,12(10):800-4.
[96]Figdor CG, Bont WS, Touw I, et al. Isolation of functionally different human monocytes by counterflow centrifugation elutriation[J]. Blood,1982,60(1): 46-53.
[97]Akiyama Y, Miller PJ, Thurman GB, et al. Characterization of a human blood monocyte subset with low peroxidase activity[J]. J Clin Invest,1983,72(3): 1093-105.
[98]Akiyama Y, Stevenson GW, Schlick E, et al. Differential ability of human blood monocyte subsets to release various cytokines[J]. J Leukoc Biol,1985, 37(5):519-30.
[99]Elias JA, Chien P, Gustilo KM, et al. Differential interleukin-1 elaboration by density-defined human monocyte subpopulations[J]. Blood,1985,66(2): 298-301.
[100]Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood[J]. Blood,1989,74(7):2527-34.
[101]Ancuta P, Rao R, Moses A, et al. Fractalkine preferentially mediates arrest and migration of CD 16+ monocytes[J]. J Exp Med,2003,197(12):1701-7.
[102]Ziegler-Heitbrock HW, Strobel M, Kieper D, et al. Differential expression of cytokines in human blood monocyte subpopulations[J]. Blood,1992,79(2): 503-11.
[103]Weber C, Belge KU, von Hundelshausen P, et al. Differential chemokine receptor expression and function in human monocyte subpopulations[J]. J Leukoc Biol,2000,67(5):699-704.
[104]Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions[J]. J Exp Med,2007,204(12):3037-47.
[105]Ziegler-Heitbrock HW. Definition of human blood monocytes[J]. J Leukoc Biol,2000,67(5):603-6.
[106]Beige KU, Dayyani F, Horelt A, et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF[J]. J Immunol,2002,168(7):3536-42.
[107]Zhao C, Zhang H, Wong WC, et al. Identification of novel functional differences in monocyte subsets using proteomic and transcriptomic methods[J]. J Proteome Res,2009,8(8):4028-38.
[108]Mobley JL, Leininger M, Madore S, et al. Genetic evidence of a functional monocyte dichotomy[J]. Inflammation,2007,30(6):189-97.
[109]Ingersoll MA, Spanbroek R, Lottaz C, et al. Comparison of gene expression profiles between human and mouse monocyte subsets[J]. Blood,2010,115(3): e10-9.
[110]Cros J, Cagnard N, Woollard K, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors[J]. Immunity,2010,33(3):375-86.
[111]Ancuta P, Liu KY, Misra V, et al. Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+and CD 16-monocyte subsets [J]. BMC Genomics,2009,10(403.
[112]Fingerle-Rowson G, Auers J, Kreuzer E, et al. Expansion of CD14+CD16+ monocytes in critically ill cardiac surgery patients[J]. Inflammation,1998, 22(4):367-79.
[113]Horelt A, Belge KU, Steppich B, et al. The CD14+CD16+monocytes in erysipelas are expanded and show reduced cytokine production[J]. Eur J Immunol,2002,32(5):1319-27.
[114]Skrzeczynska-Moncznik J, Bzowska M, Loseke S, et al. Peripheral blood CD14high CD 16+ monocytes are main producers of IL-10[J]. Scand J Immunol,2008,67(2):152-9.
[115]Schakel K, von Kietzell M, Hansel A, et al. Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes[J]. Immunity,2006,24(6): 767-77.
[116]Grage-Griebenow E, Zawatzky R, Kahlert H, et al. Identification of a novel dendritic cell-like subset of CD64(+)/CD16(+) blood monocytes[J]. Eur J Immunol,2001,31(1):48-56.
[117]Cermak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor[J]. Blood,1993,82(2): 513-20.
[118]Zawada AM. Rogacev KS, Rotter B, et al. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset[J]. Blood,2011, 118(12):e50-61.
[119]Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2[J]. Nat Immunol,2006,7(3):311-7.
[120]Sunderkotter C, Nikolic T, Dillon MJ, et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response[J]. J Immunol,2004,172(7):4410-7.
[121]Tacke F, Alvarez D, Kaplan TJ, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques[J]. J Clin Invest,2007,117(1):185-94.
[122]Jia T, Serbina NV, Brandl K, et al. Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection[J]. J Immunol,2008,180(10):6846-53.
[123]Barbalat R, Lau L, Locksley RM, et al. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands[J]. Nat Immunol,2009,10(11):1200-7.
[124]Fogg DK, Sibon C, Miled C, et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells[J]. Science,2006,311(5757): 83-7.
[125]Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. Nomenclature of monocytes and dendritic cells in blood[J]. Blood,2010,116(16):e74-80.
[126]Murdoch C, Tazzyman S, Webster S, et al. Expression of Tie-2 by human monocytes and their responses to angiopoietin-2[J]. J Immunol,2007,178(11): 7405-11.
[127]Venneri MA, De Palma M, Ponzoni M. et al. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer[J]. Blood,2007,109(12):5276-85.
[128]Lewis CE, De Palma M, Naldini L. Tie2-expressing monocytes and tumor angiogenesis:regulation by hypoxia and angiopoietin-2[J]. Cancer Res,2007, 67(18):8429-32.
[129]Coffelt SB, Tal AO, Scholz A, et al. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions[J]. Cancer Res,2010,70(13):5270-80.
[130]Coffelt SB, Chen YY, Muthana M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion[J]. J Immunol,2011,186(7):4183-90.
[131]Schakel K, Kannagi R, Kniep B, et al.6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells[J]. Immunity,2002,17(3):289-301.
[132]de Baey A, Mende I, Riethmueller G, et al. Phenotype and function of human dendritic cells derived from M-DC8(+) monocytes[J]. Eur J Immunol,2001, 31(6):1646-55.
[133]Wong KL, Tai JJ, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets[J]. Blood,2011,118(5):e16-31.
[134]de Baey A, Mende I, Baretton G, et al. A subset of human dendritic cells in the T cell area of mucosa-associated lymphoid tissue with a high potential to produce TNF-alpha[J]. J Immunol,2003,170(10):5089-94.
[135]Hansel A, Gunther C, Ingwersen J, et al. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses[J]. J Allergy Clin Immunol,2011,127(3): 787-94 e1-9.
[136]Nagasawa T, Kobayashi H, Aramaki M, et al. Expression of CD 14, CD 16 and CD45RA on monocytes from periodontitis patients[J]. J Periodontal Res,2004, 39(1):72-8.
[137]Rodriguez-Munoz Y, Martin-Vilchez S, Lopez-Rodriguez R, et al. Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C[J]. Aliment Pharmacol Ther,2011,34(8):960-71.
[138]Berg KE, Ljungcrantz I, Andersson L, et al. Elevated CD14++CD16-monocytes predict cardiovascular events[J]. Circ Cardiovasc Genet,2012,5(1): 122-31.
[139]Schlitt A, Heine GH, Blankenberg S, et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels[J]. Thromb Haemost,2004,92(2):419-24.
[140]Hristov M, Leyendecker T, Schuhmann C, et al. Circulating monocyte subsets and cardiovascular risk factors in coronary artery disease[J]. Thromb Haemost,2010,104(2):412-4.
[141]Rogacev KS, Ulrich C, Blomer L, et al. Monocyte heterogeneity in obesity and subclinical atherosclerosis[J]. Eur Heart J,2010,31(3):369-76.
[142]Kashiwagi M, Imanishi T. Tsujioka H, et al. Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris[J]. Atherosclerosis,2010,212(1):171-6.
[143]Imanishi T, Ikejima H, Tsujioka H, et al. Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris[J]. Atherosclerosis,2010,212(2):628-35.
[144]Liu Y, Imanishi T, Ikejima H, et al. Association between circulating monocyte subsets and in-stent restenosis after coronary stent implantation in patients with ST-elevation myocardial infarction[J]. Circ J,2010,74(12):2585-91.
[145]Heine GH, Ulrich C, Seibert E, et al. CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients[J]. Kidney Int,2008,73(5):622-9.
[146]Rogacev KS, Ziegelin M, Ulrich C, et al. Haemodialysis-induced transient CD 16+ monocytopenia and cardiovascular outcome[J]. Nephrol Dial Transplant,2009,24(11):3480-6.
[147]Fingerle G, Pforte A, Passlick B, et al. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients[J]. Blood,1993,82(10): 3170-6.
[148]Grip O, Bredberg A, Lindgren S, et al. Increased subpopulations of CD16(+) and CD56(+) blood monocytes in patients with active Crohn's disease[J]. Inflamm Bowel Dis,2007,13(5):566-72.
[149]Katayama K, Matsubara T, Fujiwara M, et al. CD14+CD16+ monocyte subpopulation in Kawasaki disease[J]. Clin Exp Immunol,2000,121(3): 566-70.
[150]Kawanaka N, Yamamura M, Aita T, et al. CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis[J]. Arthritis Rheum,2002, 46(10):2578-86.
[151]Soares G, Barral A, Costa JM, et al. CD 16+ monocytes in human cutaneous leishmaniasis:increased ex vivo levels and correlation with clinical data[J]. J Leukoc Biol,2006,79(1):36-9.
[152]Thieblemont N, Weiss L, Sadeghi HM, et al. CD141owCD16high:a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection[J]. Eur J Immunol,1995,25(12):3418-24.
[153]Vanham G, Edmonds K, Qing L, et al. Generalized immune activation in pulmonary tuberculosis:co-activation with HIV infection[J]. Clin Exp Immunol,1996,103(1):30-4.
[154]Szaflarska A, Baj-Krzyworzeka M, Siedlar M, et al. Antitumor response of CD14+/CD16+ monocyte subpopulation[J]. Exp Hematol,2004,32(8): 748-55.
[155]Steppich B, Dayyani F, Gruber R, et al. Selective mobilization of CD14(+)CD16(+) monocytes by exercise[J]. Am J Physiol Cell Physiol,2000, 279(3):C578-86.
[156]Ancuta P, Wang J, Gabuzda D. CD 16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells[J]. J Leukoc Biol,2006,80(5):1156-64.
[157]Rogacev KS, Seiler S, Zawada AM, et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease[J]. Eur Heart J,2011,32(1):84-92.
[158]Ulrich C, Heine GH, Seibert E, et al. Circulating monocyte subpopulations with high expression of angiotensin-converting enzyme predict mortality in patients with end-stage renal disease[J]. Nephrol Dial Transplant,2010,25(7): 2265-72.
[159]Afzal AR, Kiechl S, Daryani YP, et al. Common CCR5-del32 frameshift mutation associated with serum levels of inflammatory markers and cardiovascular disease risk in the Bruneck population[J]. Stroke,2008,39(7): 1972-8.
[160]Gonzalez P, Alvarez R, Batalla A, et al. Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction[J]. Genes Immun,2001,2(4): 191-5.
[161]Pai JK, Kraft P, Cannuscio CC, et al. Polymorphisms in the CC-chemokine receptor-2 (CCR2) and-5 (CCR5) genes and risk of coronary heart disease among US women[J]. Atherosclerosis,2006,186(1):132-9.
[162]Koenen RR, von Hundelshausen P, Nesmelova IV, et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice[J]. Nat Med,2009,15(1):97-103.
[163]Veillard NR, Kwak B, Pelli G, et al. Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice[J]. Circ Res,2004,94(2): 253-61.
[164]Muntinghe FL, Gross S, Bakker SJ, et al. CCR5Delta32 genotype is associated with outcome in type 2 diabetes mellitus[J]. Diabetes Res Clin Pract,2009,86(2):140-5.
[165]Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alphafJ]. J Exp Med,1994,179(4):1109-18.
[166]Evans HG, Gullick NJ, Kelly S, et al. In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses[J]. Proc Natl Acad Sci U S A,2009,106(15):6232-7.
[167]Wong KL, Yeap WH, Tai JJ, et al. The three human monocyte subsets: implications for health and disease[J]. Immunol Res.2012.
[168]Audoy-Remus J, Richard JF, Soulet D, et al. Rod-Shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2[J]. J Neurosci,2008,28(41):10187-99.
[2]Intersalt:an international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and, potassium excretion. Intersalt Cooperative Research Group[J]. BMJ,1988,297(6644):319-28.
[3]Mimran A, du Cailar G. Dietary sodium:the dark horse amongst cardiovascular and renal risk factors[J]. Nephrol Dial Transplant,2008,23(7): 2138-41.
[4]Gao F, Han ZQ, Zhou X, et al. High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats:time window of left ventricular functional transition and its relation to salt-loading doses[J]. Clin Exp Hypertens,2011, 33(7):492-9.
[5]Lin L, Phillips WE, Manning RD. Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension[J]. J Am Soc Hypertens,2009,3(5):306-14.
[6]Boesen El, Williams DL, Pollock JS, et al. Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats[J]. Clin Exp Pharmacol Physiol,2010,37(10):1016-22.
[7]Poitou C, Dalmas E, Renovato M, et al. CD14dimCD16+ and CD14+CD16+ monocytes in obesity and during weight loss:relationships with fat mass and subclinical atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2011,31(10): 2322-30.
[8]Tapp LD, Shantsila E, Wrigley BJ, et al. The CD14++CD16+ monocyte subset and monocyte-platelet interactions in patients with ST-elevation myocardial infarction[J]. J Thromb Haemost,2011,
[9]Tsujioka H, Imanishi T, Ikejima H, et al. Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction[J]. J Am Coll Cardiol,2009,54(2):130-8.
[10]Mantovani A, Garlanda C, Locati M. Macrophage diversity and polarization in atherosclerosis:a question of balance[J]. Arterioscler Thromb Vasc Biol,2009,29(10):1419-23.
[11]Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions[J]. J Exp Med,2007,204(12):3037-47.
[12]Furman MI, Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction[J]. J Am Coll Cardiol,2001,38(4):1002-6.
[13]Kuckleburg CJ, Yates CM, Kalia N, et al. Endothelial cell-borne platelet bridges selectively recruit monocytes in human and mouse models of vascular inflammation[J]. Cardiovasc Res,2011,91(1):134-41.
[14]Simon DI, Ezratty AM, Francis SA, et al. Fibrin(ogen) is internalized and degraded by activated human monocytoid cells via Mac-1 (CD11b/CD18):a nonplasmin fibrinolytic pathway[J]. Blood,1993,82(8):2414-22.
[15]van Gils JM, da Costa Martins PA, Mol A, et al. Transendothelial migration drives dissociation of plateletmonocyte complexes[J]. Thromb Haemost,2008, 100(2):271-9.
[16]Auffray C, Sieweke MH, Geissmann F. Blood monocytes:development, heterogeneity, and relationship with dendritic cells[J]. Annu Rev Immunol,2009,27(669-92.
[17]Woollard KJ, Geissmann F. Monocytes in atherosclerosis:subsets and functions[J]. Nat Rev Cardiol,2010,7(2):77-86.
[18]Geissmann F, Gordon S, Hume DA, et al. Unravelling mononuclear phagocyte heterogeneity[J]. Nat Rev Immunol,2010,10(453-460.
[19]Wong KL, Yeap WH, Tai JJ, et al. The three human monocyte subsets: implications for health and disease[J]. Immunol Res,2012,
[20]Hristov M, Leyendecker T, Schuhmann C, et al. Circulating monocyte subsets and cardiovascular risk factors in coronary artery disease[J]. Thromb Haemost,2010,104(2):412-4.
[21]Kashiwagi M, Imanishi T, Tsujioka H, et al. Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris[J]. Atherosclerosis,2010,212(1):171-6.
[22]Heine GH, Ulrich C, Seibert E, et al. CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients[J]. Kidney Int,2008,73(5):622-9.
[23]Rogacev KS, Ziegelin M, Ulrich C, et al. Haemodialysis-induced transient CD 16+ monocytopenia and cardiovascular outcome[J]. Nephrol Dial Transplant,2009,24(11):3480-6.
[24]Keating FK, Dauerman HL, Whitaker DA, et al. Increased expression of platelet P-selectin and formation of platelet-leukocyte aggregates in blood from patients treated with unfractionated heparin plus eptifibatide compared with bivalirudin[J]. Thromb Res,2006,118(3):361-9.
[25]Wang J, Zhang S, Jin Y, et al. Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome[J]. International Journal of Cardiology,2007,115(361-365.
[26]Michelson AD. Barnard MR, Krueger LA, et al. Circulating monocyte-platelet aggregates are a more sensitive marker of in vivo platelet activation than platelet surface P-selectin:studies in baboons, human coronary intervention, and human acute myocardial infarction[J]. Circulation,2001,104(13):1533-7.
[27]Gremmela T, Koppa C, Seidingera D, et al. The formation of monocyte-platelet aggregates is independent of on-treatment residual agonists-inducible platelet reactivity[J]. Atherosclerosis,2009,207(608-613.
[28]WHO. Reading Salt intake in population[A]. in report of a WHO Forum and Technical Meeting 5-7 October,2006 Paris, France. Switzerland:World Health Orgnization,2007:1-65.
[29]Zhou X, Liu JX. Shi R, et al. Compound ion salt, a novel low-sodium salt substitute:from animal study to community-based population trial [J]. Am J Hypertens,2009,22(9):934-42.
[30]Rogacev KS, Seiler S, Zawada AM, et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease[J]. Eur Heart J,2011,32(1):84-92.
[31]Gu D, Kelly TN, Hixson JE, et al. Genetic variants in the renin-angiotensin-aldosterone system and salt sensitivity of blood pressure [J]. J Hypertens,2010,28(6):1210-20.
[32]Hall JE, Mizelle HL, Hildebrandt DA, et al. Abnormal pressure natriuresis. A cause or a consequence of hypertension?[J]. Hypertension,1990,15(6 Pt 1): 547-59.
[33]de Wardener HE, MacGregor GA. The natriuretic hormone and essential hypertension [J]. Lancet,1982,1(8287):1450-4.
[34]Orlov SN, Mongin AA. Salt-sensing mechanisms in blood pressure regulation and hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(4): H2039-53.
[35]Sacks FM, Obarzanek E, Windhauser MM, et al. Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure[J]. Ann Epidemiol,1995,5(2):108-18.
[36]Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group[J]. N Engl J Med,2001,344(1):3-10.
[37]Weinberger MH, Fineberg NS, Fineberg SE, et al. Salt sensitivity, pulse pressure, and death in normal and hypertensive humans[J]. Hypertension,2001, 37(2 Part 2):429-32.
[38]Blaustein MP, Leenen FH, Chen L, et al. How NaCl raises blood pressure:a new paradigm for the pathogenesis of salt-dependent hypertension[J]. Am J Physiol Heart Circ Physiol,2012,302(5):H1031-49.
[39]Sakai RR, McEwen BS, Fluharty SJ, et al. The amygdala:site of genomic and nongenomic arousal of aldosterone-induced sodium intake[J]. Kidney Int,2000,57(4):1337-45.
[40]Davern PJ, Nguyen-Huu TP, La Greca L, et al. Role of the sympathetic nervous system in Schlager genetically hypertensive mice[J]. Hypertension,2009,54(4):852-9.
[41]Santos RA, Ferreira AJ, Simoes ESAC. Recent advances in the angiotensin-converting enzyme 2-angiotensin(1-7)-Mas axis[J]. Exp Physiol,2008,93(5):519-27.
[42]Oudit GY, Herzenberg AM, Kassiri Z, et al. Loss of angiotensin-converting enzyme-2 leads to the late development of angiotensin Ⅱ-dependent glomerulosclerosis[J]. Am J Pathol,2006,168(6):1808-20.
[43]Hernandez Prada JA, Ferreira AJ, Katovich MJ, et al. Structure-based identification of small-molecule angiotensin-converting enzyme 2 activators as novel antihypertensive agents[J]. Hypertension,2008,51(5):1312-7.
[44]Liu CX, Hu Q, Wang Y, et al. Angiotensin-converting enzyme (ACE) 2 overexpression ameliorates glomerular injury in a rat model of diabetic nephropathy:a comparison with ACE inhibition[J]. Mol Med,2011,17(1-2): 59-69.
[45]Huang BS, White RA, Bi L, et al. Central infusion of aliskiren prevents sympathetic hyperactivity and hypertension in Dahl salt-sensitive rats on high salt intake[J]. Am J Physiol Regul Integr Comp Physiol,2012,302(7): R825-32.
[46]Davern PJ, Head GA. Fos-related antigen immunoreactivity after acute and chronic angiotensin Ⅱ-induced hypertension in the rabbit brain[J]. Hypertension,2007,49(5):1170-7.
[47]刘治全,牟建军,李玉明.盐敏感性高血压[M].北京：人民卫生出版社,2011：166-170.
[48]Agarwal MK, Mirshahi F, Mirshahi M, et al. Immunochemical detection of the mineralocorticoid receptor in rat brain[J]. Neuroendocrinology.1993,58(5): 575-80.
[49]Franco M, Martinez F, Rodriguez-Iturbe B, et al. Angiotensin Ⅱ, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension[J]. Am J Physiol Renal Physiol,2006,291(6):F1281-7.
[50]Kobori H, Prieto-Carrasquero MC, Ozawa Y, et al. AT1 receptor mediated augmentation of intrarenal angiotensinogen in angiotensin Ⅱ-dependent hypertension[J]. Hypertension,2004,43(5):1126-32.
[51]Nishiyama A, Yoshizumi M, Rahman M, et al. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats[J]. Kidney Int,2004,65(3):972-81.
[52]Hayakawa H, Coffee K, Raij L. Endothelial dv.sfunction and cardiorenal injury in experimental salt-sensitive hypertension:effects of antihypertensive therapy [J]. Circulation,1997,96(7):2407-13.
[53]Kodama K, Adachi H, Sonoda J. Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension[J]. J Pharmacol Exp Ther,1997,283(2):625-9.
[54]Zhou MS, Adam AG, Jaimes EA, et al. In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin Ⅱ[J]. Hypertension,2003,42(5):945-51.
[55]Jaimes EA. Zhou MS, Pearse DD, et al. Upregulation of cortical COX-2 in salt-sensitive hypertension:role of angiotensin Ⅱ and reactive oxygen species[J]. Am J Physiol Renal Physiol,2008,294(2):F385-92.
[56]Banes-Berceli AK, Al-Azawi H, Proctor D, et al. Angiotensin Ⅱ utilizes Janus kinase 2 in hypertension, but not in the physiological control of blood pressure, during low-salt intake[J]. Am J Physiol Regul Integr Comp Physiol,2011, 301(4):R1169-76.
[57]Bernardi S, Toffoli B, Zennaro C, et al. High-salt diet increases glomerular ACE/ACE2 ratio leading to oxidative stress and kidney damage[J]. Nephrol Dial Transplant,2011,
[58]Bader M. Tissue renin-angiotensin-aldosterone systems:Targets for pharmacological therapy[J]. Annu Rev Pharmacol Toxicol,2010,50(439-65.
[59]Hoogwerf BJ. Renin-angiotensin system blockade and cardiovascular and renal protection [J]. Am J Cardiol,2010,105(1 Suppl):30A-5A.
[60]Nakamura T, Kataoka K, Tokutomi Y, et al. Novel mechanism of salt-induced glomerular injury:critical role of eNOS and angiotensin II[J]. J Hypertens,2011,29(8):1528-35.
[61]Chandramohan G, Bai Y, Norris K, et al. Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-kappaB activity in salt-sensitive and -resistant rat kidneys[J]. Am J Nephrol,2008,28(1):158-67.
[62]Otsuka F, Yamauchi T, Kataoka H, et al. Effects of chronic inhibition of ACE and AT1 receptors on glomerular injury in dahl salt-sensitive rats[J]. Am J Physiol,1998,274(6 Pt 2):R1797-806.
[63]Varagic J, Ahmad S, Brosnihan KB, et al. Salt-induced renal injury in spontaneously hypertensive rats:effects of nebivolol[J]. Am J Nephrol,2010, 32(6):557-66.
[64]Funder JW, Mihailidou AS. Aldosterone and mineralocorticoid receptors: Clinical studies and basic biology[J]. Mol Cell Endocrinol,2009,301(1-2): 2-6.
[65]Schiffrin EL. Effects of aldosterone on the vasculature[J]. Hypertension,2006, 47(3):312-8.
[66]Bunda S, Liu P, Wang Y, et al. Aldosterone induces elastin production in cardiac fibroblasts through activation of insulin-like growth factor-Ⅰ receptors in a mineralocorticoid receptor-independent manner[J]. Am J Pathol,2007, 171(3):809-19.
[67]Kawarazaki H, Ando K, Fujita M, et al. Mineralocorticoid receptor activation: a major contributor to salt-induced renal injury and hypertension in young rats[J]. Am J Physiol Renal Physiol,2011,300(6):F1402-9.
[68]Shibata S, Nagase M, Yoshida S, et al. Podocyte as the target for aldosterone: roles of oxidative stress and Sgk1[J]. Hypertension,2007,49(2):355-64.
[69]Pitt B. Remme W, Zannad F, et al. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction[J]. N Engl J Med,2003,348(14):1309-21.
[70]Lastra G. Whaley-Connell A, Manrique C, et al. Low-dose spironolactone reduces reactive oxygen species generation and improves insulin-stimulated glucose transport in skeletal muscle in the TG(mRen2)27 rat[J]. Am J Physiol Endocrinol Metab,2008,295(1):E110-6.
[71]Wang H, Shimosawa T, Matsui H, et al. Paradoxical mineralocorticoid receptor activation and left ventricular diastolic dysfunction under high oxidative stress conditions[J]. J Hypertens,2008,26(7):1453-62.
[72]Griendling KK, Minieri CA, Ollerenshaw JD, et al. Angiotensin Ⅱ stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells[J]. Circ Res,1994,74(6):1141-8.
[73]du Cailar G, Fesler P, Ribstein J, et al. Dietary sodium, aldosterone, and left ventricular mass changes during long-term inhibition of the renin-angiotensin system[J]. Hypertension,2010,56(5):865-70.
[74]Falkner B, Hulman S, Kushner H. Hyperinsulinemia and blood pressure sensitivity to sodium in young blacks[J]. J Am Soc Nephrol,1992,3(4):940-6.
[75]Sharma AM, Schorr U, Distler A. Insulin resistance in young salt-sensitive normotensive subjects[J]. Hypertension,1993,21(3):273-9.
[76]Weinberger MH. Salt sensitivity of blood pressure in humans[J]. Hypertension,1996,27(3 Pt 2):481-90.
[77]Chen J, Gu D, Huang J, et al. Metabolic syndrome and salt sensitivity of blood pressure in non-diabetic people in China:a dietary intervention study[J]. Lancet,2009,373(9666):829-35.
[78]Chen J. Sodium sensitivity of blood pressure in Chinese populations[J]. Curr Hypertens Rep,2010,12(2):127-34.
[79]Lastra G, Manrique C, McFarlane SI, et al. Cardiometabolic syndrome and chronic kidney disease[J]. Curr Diab Rep,2006,6(3):207-12.
[80]Saiki A, Ohira M, Endo K, et al. Circulating angiotensin Ⅱ is associated with body fat accumulation and insulin resistance in obese subjects with type 2 diabetes mellitus[J]. Metabolism,2009,58(5):708-13.
[81]Modan M, Halkin H, Almog S, et al. Hyperinsulinemia. A link between hypertension obesity and glucose intolerance[J]. J Clin Invest,1985,75(3): 809-17.
[82]Zawada AM, Rogacev KS, Rotter B, et al. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset[J]. Blood,2011, 118(12):e50-61.
[83]Tian N, Moore RS, Phillips WE, et al. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension[J]. Am J Physiol Regul Integr Comp Physiol,2008,295(6):R1858-65.
[84]Ozawa Y, Kobori H, Suzaki Y, et al. Sustained renal interstitial macrophage infiltration following chronic angiotensin Ⅱ infusions[J]. Am J Physiol Renal Physiol,2007,292(1):F330-9.
[85]Mattson DL, James L, Berdan EA, et al. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat[J]. Hypertension,2006,48(1):149-56.
[86]Tian N, Gu JW, Jordan S, et al. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,292(2):H1018-25.
[87]Tian N, Rose RA, Jordan S, et al. N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension[J]. J Hypertens,2006,24(11):2263-70.
[88]Tian N, Moore RS, Braddy S, et al. Interactions between oxidative stress and inflammation in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(6):H3388-95.
[89]Tian N, Thrasher KD, Gundy PD, et al. Antioxidant treatment prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Hypertension,2005,45(5):934-9.
[90]Crowley SD, Frey CW, Gould SK, et al. Stimulation of lymphocyte responses by angiotensin Ⅱ promotes kidney injury in hypertension[J]. Am J Physiol Renal Physiol,2008,295(2):F515-24.
[91]Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis[J]. Nature,2011,473(7347):317-25.
[92]Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options[J]. Nat Med,2011,17(11):1410-22.
[93]Hansson GK. Inflammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352(16):1685-95.
[94]Hansson GK, Libby P. The immune response in atherosclerosis:a double-edged sword[J]. Nat Rev Immunol,2006,6(7):508-19.
[95]Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood[J]. Blood,1989,74(7):2527-34.
[96]Ziegler-Heitbrock L. The CD 14+ CD 16+ blood monocytes:their role in infection and inflammation[J]. J Leukoc Biol,2007,81(3):584-92.
[97]Schlitt A, Heine GH, Blankenberg S, et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels[J]. Thromb Haemost,2004,92(2):419-24.
[98]Ancuta P, Rao R, Moses A, et al. Fractalkine preferentially mediates arrest and migration of CD16+ monocytes[J]. J Exp Med,2003,197(12):1701-7.
[99]Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets[J]. Immunobiology,2006,211(6-8):609-18.
[100]Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. Nomenclature of monocytes and dendritic cells in blood[J]. Blood,2010,116(16):e74-80.
[101]Heimbeck I, Hofer TP, Eder C, et al. Standardized single-platform assay for human monocyte subpopulations:Lower CD14+CD16++ monocytes in females[J]. Cytometry A,2010,77(9):823-30.
[102]Wong KL, Tai JJ, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets[J]. Blood,2011,118(5):e16-31.
[103]Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris[J]. Circ J,2010,74(2):337-45.
[104]Berg KE, Ljungcrantz I, Andersson L, et al. Elevated CD14++CD16-monocytes predict cardiovascular events[J]. Circ Cardiovasc Genet,2012,5(1): 122-31.
[105]Csiszar A, Wang M, Lakatta EG, et al. Inflammation and endothelial dysfunction during aging:role of NF-kappaB[J]. J Appl Physiol,2008,105(4): 1333-41.
[106]Gu JW, Tian N, Shparago M, et al. Renal NF-kappaB activation and TNF-alpha upregulation correlate with salt-sensitive hypertension in Dahl salt-sensitive rats[J]. Am J Physiol Regul Integr Comp Physiol,2006,291(6): R1817-24.
[107]Rodriguez-Iturbe B, Ferrebuz A, Vanegas V, et al. Early and sustained inhibition of nuclear factor-kappaB prevents hypertension in spontaneously hypertensive rats[J]. J Pharmacol Exp Ther,2005,315(1):51-7.
[108]Elks CM, Mariappan N, Haque M, et al. Chronic NF-{kappa}B blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR[J]. Am J Physiol Renal Physiol,2009,296(2): F298-305.
[109]Sanz-Rosa D, Oubina MP, Cediel E, et al. Effect of AT1 receptor antagonism on vascular and circulating inflammatory mediators in SHR:role of NF-kappaB/IkappaB system[J]. Am J Physiol Heart Circ Physiol,2005,288(1): H111-5.
[110]Border WA, Noble NA. Transforming growth factor beta in tissue fibrosis[J]. N Engl J Med,1994,331(19):1286-92.
[111]Yu HC, Burrell LM, Black MJ, et al. Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats[J]. Circulation,1998,98(23): 2621-8.
[112]Ying WZ, Aaron K, Wang PX, et al. Potassium inhibits dietary salt-induced transforming growth factor-beta production[J]. Hypertension,2009,54(5): 1159-63.
[113]Combadiere C, Potteaux S, Rodero M, et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice[J]. Circulation,2008,117(13):1649-57.
[114]Braunersreuther V, Zernecke A, Arnaud C, et al. Ccr5 but not Ccrl deficiency reduces development of diet-induced atherosclerosis in mice[J]. Arterioscler Thromb Vase Biol,2007,27(2):373-9.
[115]Gkaliagkousi E, Corrigall V, Becker S, et al. Decreased platelet nitric oxide contributes to increased circulating monocyte-platelet aggregates in hypertension[J]. Eur Heart J,2009,30(24):3048-54.
[116]Mickelson JK, Lakkis NM, Villarreal-Levy G, et al. Leukocyte activation with platelet adhesion after coronary angioplasty:a mechanism for recurrent disease?[J]. J Am Coll Cardiol,1996,28(2):345-53.
[117]Htun P, Fateh-Moghadam S, Tomandl B, et al. Course of platelet activation and platelet-leukocyte interaction in cerebrovascular ischemia[J]. Stroke.2006, 37(9):2283-7.
[118]Smout J, Dyker A, Cleanthis M, et al. Platelet function following acute cerebral ischemia[J]. Angiology,2009,60(3):362-9.
[119]Harding SA, Sommerfield AJ, Sarma J, et al. Increased CD40 ligand and platelet-monocyte aggregates in patients with type 1 diabetes mellitus[J]. Atherosclerosis,2004,176(2):321-5.
[120]Weyrich AS, McIntyre TM, McEver RP, et al. Monocyte tethering by P-selectin regulates monocyte chemotactic protein-1 and tumor necrosis factor-alpha secretion. Signal integration and NF-kappa B translocation[J]. J Clin Invest,1995,95(5):2297-303.
[121]Weyrich AS, Elstad MR, McEver RP, et al. Activated platelets signal chemokine synthesis by human monocytes[J]. J Clin Invest,1996,97(6): 1525-34.
[122]Dixon DA, Tolley ND, Bemis-Standoli K, et al. Expression of COX-2 in platelet-monocyte interactions occurs via combinatorial regulation involving adhesion and cytokine signaling[J]. J Clin Invest,2006,116(10):2727-38.
[123]da Costa Martins PA, van Gils JM, Mol A, et al. Platelet binding to monocytes increases the adhesive properties of monocytes by up-regulating the expression and functionality of betal and beta2 integrins[J]. J Leukoc Biol,2006,79(3):499-507.
[124]Cermak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor[J]. Blood,1993,82(2): 513-20.
[125]van der Logt CP, Dirven RJ, Reitsma PH, et al. Expression of tissue factor and tissue factor pathway inhibitor in monocytes in response to bacterial lipopolysaccharide and phorbolester[J]. Blood Coagul Fibrinolysis,1994,5(2): 211-20.
[126]Panes O, Matus V, Saez CG, et al. Human platelets synthesize and express functional tissue factor[J]. Blood,2007,109(12):5242-50.
[127]Scholz T, Temmler U, Krause S, et al. Transfer of tissue factor from platelets to monocytes:role of platelet-derived microvesicles and CD62P[J]. Thromb Haemost,2002,88(6):1033-8.
[128]Le Guyader A, Davis-Gorman G, Copeland JG, et al. A flow cytometric method for determining the binding of coagulation factor X to monocytes in whole human blood[J]. J Immunol Methods,2004,292(1-2):207-15.
[129]Kappelmayer J, Kunapuli SP, Wyshock EG, et al. Characterization of monocyte-associated factor V[J]. Thromb Haemost,1993,70(2):273-80.
[130]Satta N, Freyssinet JM, Toti F. The significance of human monocyte thrombomodulin during membrane vesiculation and after stimulation by lipopolysaccharide[J]. Br J Haematol,1997,96(3):534-42.
[131]Passacquale G, Vamadevan P, Pereira L, et al. Monocyte-platelet interaction induces a pro-inflammatory phenotype in circulating monocytes[J]. PLoS One,2011,6(10):e25595.
[132]Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD:searching for the best risk marker by multivariate modeling[J]. J Am Soc Nephrol,2005, 16 Suppl 1(S83-8.
[133]Zhou MS, Schulman IH, Raij L. Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension:role of nuclear factor kappa B activation[J]. J Hypertens,2010,28(3):527-35.
[1]Auffray C, Sieweke MH, Geissmann F. Blood monocytes:development, heterogeneity, and relationship with dendritic cells[J]. Annu Rev Immunol,2009,27(669-92.
[2]Swirski FK, Nahrendorf M, Etzrodt M, et al. Identification of splenic reservoir monocytes and their deployment to inflammatory sites[J]. Science,2009, 325(5940):612-6.
[3]Geissmann F, Auffray C, Palframan R, et al. Blood monocytes:distinct subsets, how they relate to dendritic cells, and their possible roles in the regulation of T-cell responses[J]. Immunol Cell Biol,2008,86(5):398-408.
[4]Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties[J]. Immunity,2003,19(1):71-82.
[5]Serbina NV, Jia T, Hohl TM, et al. Monocyte-mediated defense against microbial pathogens[J]. Annu Rev Immunol,2008,26(421-52.
[6]Strauss-Ayali D, Conrad SM, Mosser DM. Monocyte subpopulations and their differentiation patterns during infection[J]. J Leukoc Biol,2007,82(2):244-52.
[7]Grage-Griebenow E, Flad HD, Ernst M. Heterogeneity of human peripheral blood monocyte subsets[J]. J Leukoc Biol,2001,69(1):11-20.
[8]Banchereau J, Steinman RM. Dendritic cells and the control of immunity[J]. Nature,1998,392(6673):245-52.
[9]Tacke F, Randolph GJ. Migratory fate and differentiation of blood monocyte subsets[J]. Immunobiology,2006,211(6-8):609-18.
[10]Varol C, Yona S, Jung S. Origins and tissue-context-dependent fates of blood monocytes[J]. Immunol Cell Biol,2009,87(1):30-8.
[11]Luft FC, Mervaala E, Muller DN, et al. Hypertension-induced end-organ damage:A new transgenic approach to an old problem[J]. Hypertension,1999, 33(1 Pt 2):212-8.
[12]Bautista LE. Inflammation, endothelial dysfunction, and the risk of high blood pressure:epidemiologic and biological evidence[J]. J Hum Hypertens,2003, 17(4):223-30.
[13]Granger DN, Vowinkel T, Petnehazy T. Modulation of the inflammatory response in cardiovascular disease[J]. Hypertension,2004,43(5):924-31.
[14]Ikejima H, Imanishi T, Tsujioka H, et al. Upregulation of fractalkine and its receptor, CX3CR1, is associated with coronary plaque rupture in patients with unstable angina pectoris[J]. Circ J,2010,74(2):337-45.
[15]Tripepi G, Mallamaci F, Zoccali C. Inflammation markers, adhesion molecules, and all-cause and cardiovascular mortality in patients with ESRD:searching for the best risk marker by multivariate modeling[J]. J Am Soc Nephrol,2005, 16Suppl1(S83-8.
[16]Kim F, Pham M, Luttrell I, et al. Toll-like receptor-4 mediates vascular inflammation and insulin resistance in diet-induced obesity[J]. Circ Res,2007, 100(11):1589-96.
[17]Boyle PJ. Diabetes mellitus and macrovascular disease:mechanisms and mediators[J]. Am J Med,2007,120(9 Suppl 2):S12-7.
[18]Svendsen UG. Evidence for an initial, thymus independent and a chronic, thymus dependent phase of DOCA and salt hypertension in mice[J]. Acta Pathol Microbiol Scand A,1976,84(6):523-8.
[19]Bataillard A, Freiche JC, Vincent M, et al. Antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat[J]. Thymus,1986,8(6): 321-30.
[20]Bataillard A, Renaudin C, Sassard J. Silica attenuates hypertension in Lyon hypertensive rats[J]. J Hypertens,1995,13(12 Pt 2):1581-4.
[21]Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin Ⅱ induced hypertension and vascular dysfunction [J]. J Exp Med,2007,204(10):2449-60.
[22]Rodriguez-Iturbe B, Quiroz Y, Nava M, et al. Reduction of renal immune cell infiltration results in blood pressure control in genetically hypertensive rats[J]. Am J Physiol Renal Physiol,2002,282(2):F191-201.
[23]Alvarez V, Quiroz Y, Nava M, et al. Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells[J]. Am J Physiol Renal Physiol,2002,283(5):F1132-41.
[24]Vanegas V, Ferrebuz A, Quiroz Y, et al. Hypertension in Page (cellophane-wrapped) kidney is due to interstitial nephritis[J]. Kidney Int,2005,68(3):1161-70.
[25]Stewart T, Jung FF, Manning J, et al. Kidney immune cell infiltration and oxidative stress contribute to prenatally programmed hypertension[J]. Kidney Int,2005,68(5):2180-8.
[26]Mattson DL, James L, Berdan EA, et al. Immune suppression attenuates hypertension and renal disease in the Dahl salt-sensitive rat[J]. Hypertension,2006,48(1):149-56.
[27]Tian N, Gu JW, Jordan S, et al. Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,292(2):H1018-25.
[28]Crowley SD, Frey CW, Gould SK, et al. Stimulation of lymphocyte responses by angiotensin Ⅱ promotes kidney injury in hypertension[J]. Am J Physiol Renal Physiol,2008,295(2):F515-24.
[29]Pechman KR, Basile DP, Lund H, et al. Immune suppression blocks sodium-sensitive hypertension following recovery from ischemic acute renal failure[J]. Am J Physiol Regul Integr Comp Physiol,2008,294(4):R1234-9.
[30]Seaberg EC, Munoz A, Lu M, et al. Association between highly active antiretroviral therapy and hypertension in a large cohort of men followed from 1984 to 2003[J]. AIDS,2005,19(9):953-60.
[31]Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis[J]. Nature,2011,473(7347):317-25.
[32]Weber C, Noels H. Atherosclerosis:current pathogenesis and therapeutic options[J]. Nat Med,2011,17(11):1410-22.
[33]Woollard KJ, Geissmann F. Monocytes in atherosclerosis:subsets and functions[J]. Nat Rev Cardiol,2010,7(2):77-86.
[34]Hansson GK. Inflammation, atherosclerosis, and coronary artery disease[J]. N Engl J Med,2005,352(16):1685-95.
[35]Hansson GK, Libby P. The immune response in atherosclerosis:a double-edged sword[J]. Nat Rev Immunol,2006,6(7):508-19.
[36]Shah PK. Molecular mechanisms of plaque instability[J]. Curr Opin Lipidol,2007,18(5):492-9.
[37]Johnson-Tidey RR, McGregor JL, Taylor PR, et al. Increase in the adhesion molecule P-selectin in endothelium overlying atherosclerotic plaques. Coexpression with intercellular adhesion molecule-1[J]. Am J Pathol,1994, 144(5):952-61.
[38]Woollard KJ. Chin-Dusting J. Therapeutic targeting of p-selectin in atherosclerosis[J]. Inflamm Allergy Drug Targets,2007,6(1):69-74.
[39]Johnson RC, Chapman SM, Dong ZM, et al. Absence of P-selectin delays fatty streak formation in mice[J]. J Clin Invest,1997,99(5):1037-43.
[40]Dong ZM, Chapman SM, Brown AA, et al. The combined role of P- and E-selectins in atherosclerosis [J]. J Clin Invest,1998,102(1):145-52.
[41]Galkina E, Ley K. Vascular adhesion molecules in atherosclerosis[J]. Arterioscler Thromb Vasc Biol,2007,27(11):2292-301.
[42]Nageh MF, Sandberg ET, Marotti KR, et al. Deficiency of inflammatory cell adhesion molecules protects against atherosclerosis in mice[J]. Arterioscler Thromb Vasc Biol,1997,17(8):1517-20.
[43]Cybulsky MI, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis[J]. J Clin Invest,2001,107(10):1255-62.
[44]Girard JP, Springer TA. High endothelial venules (HEVs):specialized endothelium for lymphocyte migration[J]. Immunol Today,1995,16(9): 449-57.
[45]Qu C, Edwards EW, Tacke F, et al. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes[J]. J Exp Med,2004,200(10):1231-41.
[46]Combadiere C, Potteaux S, Rodero M, et al. Combined inhibition of CCL2, CX3CR1, and CCR5 abrogates Ly6C(hi) and Ly6C(lo) monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice[J]. Circulation,2008,117(13):1649-57.
[47]Saederup N, Chan L, Lira SA, et al. Fractalkine deficiency markedly reduces macrophage accumulation and atherosclerotic lesion formation in CCR2-/- mice:evidence for independent chemokine functions in atherogenesis[J]. Circulation,2008,117(13):1642-8.
[48]Lesnik P, Haskell CA, Charo IF. Decreased atherosclerosis in CX3CR1-/-mice reveals a role for fractalkine in atherogenesis[J]. J Clin Invest,2003, 111(3):333-40.
[49]Smith JD, Trogan E, Ginsberg M, et al. Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E[J]. Proc Natl Acad Sci U S A,1995,92(18):8264-8.
[50]Qiao JH, Tripathi J, Mishra NK, et al. Role of macrophage colony-stimulating factor in atherosclerosis:studies of osteopetrotic mice[J]. Am J Pathol,1997, 150(5):1687-99.
[51]Ulrich C, Heine GH, Garcia P, et al. Increased expression of monocytic angiotensin-converting enzyme in dialysis patients with cardiovascular disease[J]. Nephrol Dial Transplant,2006,21(6):1596-602.
[52]Llodra J, Angeli V, Liu J, et al. Emigration of monocyte-derived cells from atherosclerotic lesions characterizes regressive, but not progressive, plaques[J]. Proc Natl Acad Sci U S A,2004,101(32):11779-84.
[53]Feig JE, Quick JS, Fisher EA. The role of a murine transplantation model of atherosclerosis regression in drug discovery[J]. Curr Opin Investig Drugs,2009,10(3):232-8.
[54]Guyton AC, Coleman TG, Cowley AV, Jr., et al. Arterial pressure regulation. Overriding dominance of the kidneys in long-term regulation and in hypertension[J]. Am J Med,1972,52(5):584-94.
[55]Franco M, Martinez F, Quiroz Y, et al. Renal angiotensin Ⅱ concentration and interstitial infiltration of immune cells are correlated with blood pressure levels in salt-sensitive hypertension[J]. Am J Physiol Regul Integr Comp Physiol,2007,293(1):R251-6.
[56]Tian N, Moore RS, Phillips WE, et al. NADPH oxidase contributes to renal damage and dysfunction in Dahl salt-sensitive hypertension [J]. Am J Physiol Regul Integr Comp Physiol,2008,295(6):R1858-65.
[57]Ozawa Y, Kobori H, Suzaki Y, et al. Sustained renal interstitial macrophage infiltration following chronic angiotensin Ⅱ infusions[J]. Am J Physiol Renal Physiol,2007,292(1):F330-9.
[58]Tian N, Rose RA, Jordan S, et al. N-Acetylcysteine improves renal dysfunction, ameliorates kidney damage and decreases blood pressure in salt-sensitive hypertension[J]. J Hypertens,2006,24(11):2263-70.
[59]Tian N, Moore RS, Braddy S, et al. Interactions between oxidative stress and inflammation in salt-sensitive hypertension[J]. Am J Physiol Heart Circ Physiol,2007,293(6):H3388-95.
[60]Tian N, Thrasher KD, Gundy PD, et al. Antioxidant treatment prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension[J]. Hypertension,2005,45(5):934-9.
[61]Allcock GH, Venema RC, Pollock DM. ETA receptor blockade attenuates the hypertension but not renal dysfunction in DOCA-salt rats[J]. Am J Physiol,1998,275(1 Pt 2):R245-52.
[62]Hayakawa H, Coffee K, Raij L. Endothelial dysfunction and cardiorenal injury in experimental salt-sensitive hypertension:effects of antihypertensive therapy[J]. Circulation,1997,96(7):2407-13.
[63]Kodama K, Adachi H, Sonoda J. Beneficial effects of long-term enalapril treatment and low-salt intake on survival rate of dahl salt-sensitive rats with established hypertension[J]. J Pharmacol Exp Ther,1997,283(2):625-9.
[64]Chandramohan G, Bai Y, Norris K, et al. Effects of dietary salt on intrarenal angiotensin system, NAD(P)H oxidase, COX-2, MCP-1 and PAI-1 expressions and NF-kappaB activity in salt-sensitive and -resistant rat kidneys[J]. Am J Nephrol,2008,28(1):158-67.
[65]Kobori H, Nangaku M, Navar LG, et al. The intrarenal renin-angiotensin system:from physiology to the pathobiology of hypertension and kidney disease[J]. Pharmacol Rev,2007,59(3):251-87.
[66]Nishiyama A, Yoshizumi M, Rahman M, et al. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats [J]. Kidney Int,2004,65(3):972-81.
[67]Zhou MS, Adam AG, Jaimes EA, et al. In salt-sensitive hypertension, increased superoxide production is linked to functional upregulation of angiotensin Ⅱ[J]. Hypertension,2003,42(5):945-51.
[68]Jaimes EA, Zhou MS, Pearse DD, et al. Upregulation of cortical COX-2 in salt-sensitive hypertension:role of angiotensin Ⅱ and reactive oxygen species[J]. Am J Physiol Renal Physiol,2008,294(2):F385-92.
[69]Lin L, Phillips WE, Manning RD. Intrarenal Angiotensin ii is associated with inflammation, renal damage and dysfunction in dahl salt-sensitive hypertension[J]. J Am Soc Hypertens,2009,3(5):306-14.
[70]Franco M, Martinez F, Rodriguez-Iturbe B, et al. Angiotensin Ⅱ, interstitial inflammation, and the pathogenesis of salt-sensitive hypertension[J]. Am J Physiol Renal Physiol,2006,291(6):F1281-7.
[71]Kobori H, Prieto-Carrasquero MC, Ozawa Y, et al. ATI receptor mediated augmentation of intrarenal angiotensinogen in angiotensin Ⅱ-dependent hypertension[J]. Hypertension,2004,43(5):1126-32.
[72]Prieto-Carrasquero MC, Kobori H, Ozawa Y, et al. ATI receptor-mediated enhancement of collecting duct renin in angiotensin Ⅱ-dependent hypertensive rats[J]. Am J Physiol Renal Physiol,2005,289(3):F632-7.
[73]Otsuka F, Yamauchi T, Kataoka H, et al. Effects of chronic inhibition of ACE and ATI receptors on glomerular injury in dahl salt-sensitive rats[J]. Am J Physiol,1998,274(6 Pt 2):R1797-806.
[74]Machnik A, Neuhofer W, Jantsch J, et al. Macrophages regulate salt-dependent volume and blood pressure by a vascular endothelial growth factor-C-dependent buffering mechanism[J]. Nat Med,2009,15(5):545-52.
[75]Weber KT, Brilla CG. Pathological hypertrophy and cardiac interstitium. Fibrosis and renin-angiotensin-aldosterone system[J]. Circulation,1991,83(6): 1849-65.
[76]Blasi ER, Rocha R, Rudolph AE, et al. Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats[J]. Kidney Int,2003,63(5): 1791-800.
[77]Rocha R, Chander PN, Khanna K, et al. Mineralocorticoid blockade reduces vascular injury in stroke-prone hypertensive rats[J]. Hypertension,1998,31(1 Pt 2):451-8.
[78]Kretzler M, Koeppen-Hagemann I, Kriz W. Podocyte damage is a critical step in the development of glomerulosclerosis in the uninephrectomised-desoxycorticosterone hypertensive rat[J]. Virchows Arch,1994,425(2):181-93.
[79]Armanini D, Endres S, Kuhnle U, et al. Parallel determination of mineralocorticoid and glucocorticoid receptors in T-and B-lymphocytes of human spleen[J]. Acta Endocrinol (Copenh),1988,118(4):479-82.
[80]Armanini D, Strasser T, Weber PC. Binding of agonists and antagonists to mineralocorticoid receptors in human peripheral mononuclear leucocytes[J]. J Hypertens Suppl,1985,3(3):S157-9.
[81]Rickard AJ, Morgan J, Tesch G, et al. Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure[J]. Hypertension,2009,54(3):537-43.
[82]Herrada AA, Contreras FJ, Marini NP, et al. Aldosterone promotes autoimmune damage by enhancing Thl7-mediated immunity [J]. J Immunol,2010,184(1):191-202.
[83]Miura R, Nakamura K, Miura D, et al. Aldosterone synthesis and cytokine production in human peripheral blood mononuclear cells[J]. J Pharmacol Sci,2006,102(3):288-95.
[84]Keidar S, Kaplan M, Pavlotzky E, et al. Aldosterone administration to mice stimulates macrophage NADPH oxidase and increases atherosclerosis development:a possible role for angiotensin-converting enzyme and the receptors for angiotensin Ⅱ and aldosterone[J]. Circulation.2004,109(18): 2213-20.
[85]Massy ZA, Guijarro C. Statins:effects beyond cholesterol lowering[J]. Nephrol Dial Transplant,2001,16(9):1738-41.
[86]Hartner A, Klanke B, Cordasic N, et al. Statin treatment reduces glomerular inflammation and podocyte damage in rat deoxycorticosterone-acetate-salt hypertension[J]. J Hypertens,2009,27(2):376-85.
[87]Blanco S, Vaquero M, Gomez-Guerrero C, et al. Potential role of angiotensin-converting enzyme inhibitors and statins on early podocyte damage in a model of type 2 diabetes mellitus, obesity, and mild hypertension[J]. Am J Hypertens,2005,18(4 Pt 1):557-65.
[88]Whaley-Connell A, DeMarco VG, Lastra G, et al. Insulin resistance, oxidative stress, and podocyte injury:role of rosuvastatin modulation of filtration barrier injury[J]. Am J Nephrol,2008,28(1):67-75.
[89]Ramirez R, Carracedo J, Soriano S, et al. Stress-induced premature senescence in mononuclear cells from patients on long-term hemodialysis[J]. Am J Kidney Dis,2005,45(2):353-9.
[90]Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection):a randomised placebo-controlled trial[J]. Lancet,2011,377(9784):2181-92.
[91]Heine GH, Ortiz A, Massy ZA, et al. Monocyte subpopulations and cardiovascular risk in chronic kidney disease[J]. Nat Rev Nephrol,2012,
[92]Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome[J]. J Am Coll Cardiol.2008,52(19):1527-39.
[93]Auffray C, Fogg D, Garfa M, et al. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior[J]. Science,2007, 317(5838):666-70.
[94]Yasaka T, Mantich NM, Boxer LA, et al. Functions of human monocyte and lymphocyte subsets obtained by countercurrent centrifugal elutriation: differing functional capacities of human monocyte subsets[J]. J Immunol,1981, 127(4):1515-8.
[95]Weiner RS, Mason RR. Subfractionation of human blood monocyte subsets with Percoll[J]. Exp Hematol,1984,12(10):800-4.
[96]Figdor CG, Bont WS, Touw I, et al. Isolation of functionally different human monocytes by counterflow centrifugation elutriation[J]. Blood,1982,60(1): 46-53.
[97]Akiyama Y, Miller PJ, Thurman GB, et al. Characterization of a human blood monocyte subset with low peroxidase activity[J]. J Clin Invest,1983,72(3): 1093-105.
[98]Akiyama Y, Stevenson GW, Schlick E, et al. Differential ability of human blood monocyte subsets to release various cytokines[J]. J Leukoc Biol,1985, 37(5):519-30.
[99]Elias JA, Chien P, Gustilo KM, et al. Differential interleukin-1 elaboration by density-defined human monocyte subpopulations[J]. Blood,1985,66(2): 298-301.
[100]Passlick B, Flieger D, Ziegler-Heitbrock HW. Identification and characterization of a novel monocyte subpopulation in human peripheral blood[J]. Blood,1989,74(7):2527-34.
[101]Ancuta P, Rao R, Moses A, et al. Fractalkine preferentially mediates arrest and migration of CD 16+ monocytes[J]. J Exp Med,2003,197(12):1701-7.
[102]Ziegler-Heitbrock HW, Strobel M, Kieper D, et al. Differential expression of cytokines in human blood monocyte subpopulations[J]. Blood,1992,79(2): 503-11.
[103]Weber C, Belge KU, von Hundelshausen P, et al. Differential chemokine receptor expression and function in human monocyte subpopulations[J]. J Leukoc Biol,2000,67(5):699-704.
[104]Nahrendorf M, Swirski FK, Aikawa E, et al. The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions[J]. J Exp Med,2007,204(12):3037-47.
[105]Ziegler-Heitbrock HW. Definition of human blood monocytes[J]. J Leukoc Biol,2000,67(5):603-6.
[106]Beige KU, Dayyani F, Horelt A, et al. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF[J]. J Immunol,2002,168(7):3536-42.
[107]Zhao C, Zhang H, Wong WC, et al. Identification of novel functional differences in monocyte subsets using proteomic and transcriptomic methods[J]. J Proteome Res,2009,8(8):4028-38.
[108]Mobley JL, Leininger M, Madore S, et al. Genetic evidence of a functional monocyte dichotomy[J]. Inflammation,2007,30(6):189-97.
[109]Ingersoll MA, Spanbroek R, Lottaz C, et al. Comparison of gene expression profiles between human and mouse monocyte subsets[J]. Blood,2010,115(3): e10-9.
[110]Cros J, Cagnard N, Woollard K, et al. Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors[J]. Immunity,2010,33(3):375-86.
[111]Ancuta P, Liu KY, Misra V, et al. Transcriptional profiling reveals developmental relationship and distinct biological functions of CD16+and CD 16-monocyte subsets [J]. BMC Genomics,2009,10(403.
[112]Fingerle-Rowson G, Auers J, Kreuzer E, et al. Expansion of CD14+CD16+ monocytes in critically ill cardiac surgery patients[J]. Inflammation,1998, 22(4):367-79.
[113]Horelt A, Belge KU, Steppich B, et al. The CD14+CD16+monocytes in erysipelas are expanded and show reduced cytokine production[J]. Eur J Immunol,2002,32(5):1319-27.
[114]Skrzeczynska-Moncznik J, Bzowska M, Loseke S, et al. Peripheral blood CD14high CD 16+ monocytes are main producers of IL-10[J]. Scand J Immunol,2008,67(2):152-9.
[115]Schakel K, von Kietzell M, Hansel A, et al. Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes[J]. Immunity,2006,24(6): 767-77.
[116]Grage-Griebenow E, Zawatzky R, Kahlert H, et al. Identification of a novel dendritic cell-like subset of CD64(+)/CD16(+) blood monocytes[J]. Eur J Immunol,2001,31(1):48-56.
[117]Cermak J, Key NS, Bach RR, et al. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor[J]. Blood,1993,82(2): 513-20.
[118]Zawada AM. Rogacev KS, Rotter B, et al. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset[J]. Blood,2011, 118(12):e50-61.
[119]Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2[J]. Nat Immunol,2006,7(3):311-7.
[120]Sunderkotter C, Nikolic T, Dillon MJ, et al. Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response[J]. J Immunol,2004,172(7):4410-7.
[121]Tacke F, Alvarez D, Kaplan TJ, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques[J]. J Clin Invest,2007,117(1):185-94.
[122]Jia T, Serbina NV, Brandl K, et al. Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection[J]. J Immunol,2008,180(10):6846-53.
[123]Barbalat R, Lau L, Locksley RM, et al. Toll-like receptor 2 on inflammatory monocytes induces type I interferon in response to viral but not bacterial ligands[J]. Nat Immunol,2009,10(11):1200-7.
[124]Fogg DK, Sibon C, Miled C, et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells[J]. Science,2006,311(5757): 83-7.
[125]Ziegler-Heitbrock L, Ancuta P, Crowe S, et al. Nomenclature of monocytes and dendritic cells in blood[J]. Blood,2010,116(16):e74-80.
[126]Murdoch C, Tazzyman S, Webster S, et al. Expression of Tie-2 by human monocytes and their responses to angiopoietin-2[J]. J Immunol,2007,178(11): 7405-11.
[127]Venneri MA, De Palma M, Ponzoni M. et al. Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer[J]. Blood,2007,109(12):5276-85.
[128]Lewis CE, De Palma M, Naldini L. Tie2-expressing monocytes and tumor angiogenesis:regulation by hypoxia and angiopoietin-2[J]. Cancer Res,2007, 67(18):8429-32.
[129]Coffelt SB, Tal AO, Scholz A, et al. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions[J]. Cancer Res,2010,70(13):5270-80.
[130]Coffelt SB, Chen YY, Muthana M, et al. Angiopoietin 2 stimulates TIE2-expressing monocytes to suppress T cell activation and to promote regulatory T cell expansion[J]. J Immunol,2011,186(7):4183-90.
[131]Schakel K, Kannagi R, Kniep B, et al.6-Sulfo LacNAc, a novel carbohydrate modification of PSGL-1, defines an inflammatory type of human dendritic cells[J]. Immunity,2002,17(3):289-301.
[132]de Baey A, Mende I, Riethmueller G, et al. Phenotype and function of human dendritic cells derived from M-DC8(+) monocytes[J]. Eur J Immunol,2001, 31(6):1646-55.
[133]Wong KL, Tai JJ, Wong WC, et al. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets[J]. Blood,2011,118(5):e16-31.
[134]de Baey A, Mende I, Baretton G, et al. A subset of human dendritic cells in the T cell area of mucosa-associated lymphoid tissue with a high potential to produce TNF-alpha[J]. J Immunol,2003,170(10):5089-94.
[135]Hansel A, Gunther C, Ingwersen J, et al. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses[J]. J Allergy Clin Immunol,2011,127(3): 787-94 e1-9.
[136]Nagasawa T, Kobayashi H, Aramaki M, et al. Expression of CD 14, CD 16 and CD45RA on monocytes from periodontitis patients[J]. J Periodontal Res,2004, 39(1):72-8.
[137]Rodriguez-Munoz Y, Martin-Vilchez S, Lopez-Rodriguez R, et al. Peripheral blood monocyte subsets predict antiviral response in chronic hepatitis C[J]. Aliment Pharmacol Ther,2011,34(8):960-71.
[138]Berg KE, Ljungcrantz I, Andersson L, et al. Elevated CD14++CD16-monocytes predict cardiovascular events[J]. Circ Cardiovasc Genet,2012,5(1): 122-31.
[139]Schlitt A, Heine GH, Blankenberg S, et al. CD14+CD16+ monocytes in coronary artery disease and their relationship to serum TNF-alpha levels[J]. Thromb Haemost,2004,92(2):419-24.
[140]Hristov M, Leyendecker T, Schuhmann C, et al. Circulating monocyte subsets and cardiovascular risk factors in coronary artery disease[J]. Thromb Haemost,2010,104(2):412-4.
[141]Rogacev KS, Ulrich C, Blomer L, et al. Monocyte heterogeneity in obesity and subclinical atherosclerosis[J]. Eur Heart J,2010,31(3):369-76.
[142]Kashiwagi M, Imanishi T. Tsujioka H, et al. Association of monocyte subsets with vulnerability characteristics of coronary plaques as assessed by 64-slice multidetector computed tomography in patients with stable angina pectoris[J]. Atherosclerosis,2010,212(1):171-6.
[143]Imanishi T, Ikejima H, Tsujioka H, et al. Association of monocyte subset counts with coronary fibrous cap thickness in patients with unstable angina pectoris[J]. Atherosclerosis,2010,212(2):628-35.
[144]Liu Y, Imanishi T, Ikejima H, et al. Association between circulating monocyte subsets and in-stent restenosis after coronary stent implantation in patients with ST-elevation myocardial infarction[J]. Circ J,2010,74(12):2585-91.
[145]Heine GH, Ulrich C, Seibert E, et al. CD14(++)CD16+ monocytes but not total monocyte numbers predict cardiovascular events in dialysis patients[J]. Kidney Int,2008,73(5):622-9.
[146]Rogacev KS, Ziegelin M, Ulrich C, et al. Haemodialysis-induced transient CD 16+ monocytopenia and cardiovascular outcome[J]. Nephrol Dial Transplant,2009,24(11):3480-6.
[147]Fingerle G, Pforte A, Passlick B, et al. The novel subset of CD14+/CD16+ blood monocytes is expanded in sepsis patients[J]. Blood,1993,82(10): 3170-6.
[148]Grip O, Bredberg A, Lindgren S, et al. Increased subpopulations of CD16(+) and CD56(+) blood monocytes in patients with active Crohn's disease[J]. Inflamm Bowel Dis,2007,13(5):566-72.
[149]Katayama K, Matsubara T, Fujiwara M, et al. CD14+CD16+ monocyte subpopulation in Kawasaki disease[J]. Clin Exp Immunol,2000,121(3): 566-70.
[150]Kawanaka N, Yamamura M, Aita T, et al. CD14+,CD16+ blood monocytes and joint inflammation in rheumatoid arthritis[J]. Arthritis Rheum,2002, 46(10):2578-86.
[151]Soares G, Barral A, Costa JM, et al. CD 16+ monocytes in human cutaneous leishmaniasis:increased ex vivo levels and correlation with clinical data[J]. J Leukoc Biol,2006,79(1):36-9.
[152]Thieblemont N, Weiss L, Sadeghi HM, et al. CD141owCD16high:a cytokine-producing monocyte subset which expands during human immunodeficiency virus infection[J]. Eur J Immunol,1995,25(12):3418-24.
[153]Vanham G, Edmonds K, Qing L, et al. Generalized immune activation in pulmonary tuberculosis:co-activation with HIV infection[J]. Clin Exp Immunol,1996,103(1):30-4.
[154]Szaflarska A, Baj-Krzyworzeka M, Siedlar M, et al. Antitumor response of CD14+/CD16+ monocyte subpopulation[J]. Exp Hematol,2004,32(8): 748-55.
[155]Steppich B, Dayyani F, Gruber R, et al. Selective mobilization of CD14(+)CD16(+) monocytes by exercise[J]. Am J Physiol Cell Physiol,2000, 279(3):C578-86.
[156]Ancuta P, Wang J, Gabuzda D. CD 16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells[J]. J Leukoc Biol,2006,80(5):1156-64.
[157]Rogacev KS, Seiler S, Zawada AM, et al. CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease[J]. Eur Heart J,2011,32(1):84-92.
[158]Ulrich C, Heine GH, Seibert E, et al. Circulating monocyte subpopulations with high expression of angiotensin-converting enzyme predict mortality in patients with end-stage renal disease[J]. Nephrol Dial Transplant,2010,25(7): 2265-72.
[159]Afzal AR, Kiechl S, Daryani YP, et al. Common CCR5-del32 frameshift mutation associated with serum levels of inflammatory markers and cardiovascular disease risk in the Bruneck population[J]. Stroke,2008,39(7): 1972-8.
[160]Gonzalez P, Alvarez R, Batalla A, et al. Genetic variation at the chemokine receptors CCR5/CCR2 in myocardial infarction[J]. Genes Immun,2001,2(4): 191-5.
[161]Pai JK, Kraft P, Cannuscio CC, et al. Polymorphisms in the CC-chemokine receptor-2 (CCR2) and-5 (CCR5) genes and risk of coronary heart disease among US women[J]. Atherosclerosis,2006,186(1):132-9.
[162]Koenen RR, von Hundelshausen P, Nesmelova IV, et al. Disrupting functional interactions between platelet chemokines inhibits atherosclerosis in hyperlipidemic mice[J]. Nat Med,2009,15(1):97-103.
[163]Veillard NR, Kwak B, Pelli G, et al. Antagonism of RANTES receptors reduces atherosclerotic plaque formation in mice[J]. Circ Res,2004,94(2): 253-61.
[164]Muntinghe FL, Gross S, Bakker SJ, et al. CCR5Delta32 genotype is associated with outcome in type 2 diabetes mellitus[J]. Diabetes Res Clin Pract,2009,86(2):140-5.
[165]Sallusto F, Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alphafJ]. J Exp Med,1994,179(4):1109-18.
[166]Evans HG, Gullick NJ, Kelly S, et al. In vivo activated monocytes from the site of inflammation in humans specifically promote Th17 responses[J]. Proc Natl Acad Sci U S A,2009,106(15):6232-7.
[167]Wong KL, Yeap WH, Tai JJ, et al. The three human monocyte subsets: implications for health and disease[J]. Immunol Res.2012.
[168]Audoy-Remus J, Richard JF, Soulet D, et al. Rod-Shaped monocytes patrol the brain vasculature and give rise to perivascular macrophages under the influence of proinflammatory cytokines and angiopoietin-2[J]. J Neurosci,2008,28(41):10187-99.