生长分化因子15与微血管病变发生机制的研究进展
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摘要
生长分化因子15(GDF-15)属于转化生长因子-β超家族,其参与多种血管生理病理改变,具有广泛的生物学作用,是一个潜在的血管内皮相关因子,与血管内皮修复、氧化应激、炎症反应、促血管增殖、启动相关信号通路等有关,在血管增殖和生理性、病理性血管生成中起到关键作用。在大血管及微血管病变疾病中,如糖尿病相关微血管并发症、心血管疾病的微循环障碍中均发现GDF-15表达的增强,影响了微血管相关病变的发生发展,并与其预后相关。因此,GDF-15与微血管病变的发生关系密切。
Growth differentiation factor-15( GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is involved in a variety of physiological and pathological changes of blood vessels,has a wide range of biological effects,and is a potential vascular endothelial-related factor. It plays an important role in vascular endothelial repair,oxidative stress,inflammatory reaction,promotion of vascular proliferation,activation of related signal pathways and other functions. It also plays a key role in vascular proliferation,physiological and pathological angiogenesis. Studies have shown that in macrovascular and microvascular diseases,such as diabetic-related microvascular complications and microcirculation disorders of cardiovascular diseases,the increased expression of GDF-15 has been found,which affects the occurrence and development of microvessel-related diseases,and is related to the prognosis. Therefore,GDF-15 is closely related to the occurrence of microangiopathy.
Growth differentiation factor-15( GDF-15) belongs to the transforming growth factor-β superfamily. GDF-15 is involved in a variety of physiological and pathological changes of blood vessels,has a wide range of biological effects,and is a potential vascular endothelial-related factor. It plays an important role in vascular endothelial repair,oxidative stress,inflammatory reaction,promotion of vascular proliferation,activation of related signal pathways and other functions. It also plays a key role in vascular proliferation,physiological and pathological angiogenesis. Studies have shown that in macrovascular and microvascular diseases,such as diabetic-related microvascular complications and microcirculation disorders of cardiovascular diseases,the increased expression of GDF-15 has been found,which affects the occurrence and development of microvessel-related diseases,and is related to the prognosis. Therefore,GDF-15 is closely related to the occurrence of microangiopathy.
引文
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[22] Tsui KH,Hsu SY,Chung LC,et al. Growth differentiation factor-15:A p53 and demethylation upregulating gene represses cell proliferation,invasion,and tumorigenesis in bladder carcinoma cells[J]. Sci Rep,2015,5:12870.
[23] Potente M,Gerhardt H,Carmeliet P. Basic and therapeutic aspects of angiogenesis[J]. Cell,2011,146(6):873-887.
[24]尚小森,卫兵艳,刘田福,等.缺氧条件下GDF-15对心肌微血管内皮细胞成管的影响[J/CD].中西医结合心血管病电子杂志,2017,5(31):56-57.
[25]李博,吴慧颖,朴虎林,等.生长分化因子5对血管内皮细胞增殖和运动的影响[J].吉林大学学报(医学版),2011,37(6):1062-1064.
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[27]阮园,王绍冠,王溢苏,等.血浆生长分化因子-15水平与2型糖尿病肾病分期的相关性研究[J].全科医学临床与教育,2018,16(2):137-140.
[28]王军,张松林,和旭梅,等.上调GDF-15表达对H2O2诱导的H9C2心肌细胞生物学特性及PI3K/AKT信号通路的影响[J].中国免疫学杂志,2018,34(5):658-664.
[29] Brown DA,Breit SN,Buring J,et al. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women:A nested case-control study[J]. Lancet,2002,359(9324):2159-6321.
[30] Arden GB,Sivaprasad S. Hypoxia and oxidative stress in the causation of diabetic retinopathy[J]. Curr Diabetes Rev,2011,7(5):291-304.
[31]刘玥明.患者血浆生长分化因子15水平与白蛋白尿及糖尿病视网膜病变关联性研究[D].上海:上海交通大学,2015.
[32] Macia L,Tsai WW,Nguyen AD,et al. Macrophage inhibitory cytokine 1(MIC-1/GDF15)decreases food intake,body weight and improves glucose tolerance in mice on normal&obesogenic diets[J]. PLoS One,2012,7(4):e34868.
[33]郭潮.血清生长分化因子-15与急性心肌梗死后左室重构程度的相关性研究[D].太原:山西医科大学,2013.
[34] Wollert KC,Kempf T,Wallentin L. Growth differentiation factor15 as a biomarker in cardiovascular disease[J]. Clin Chem,2017,63(1):140-151.
[35]贝雪艳,李军,曲忠慧,等.左心疾病相关性肺动脉高压患者血浆GDF-15 BNP的水平及意义[J].河北医学,2017,23(12):2025-2027.
[36] Kou H,Jin X,Gao D,et al. Association between growth differentiation factor 15 and left ventricular hypertrophy in hypertensive patients and healthy adults[J]. Clin Exp Hypertens,2018,40(1):8-15.
[37] Berezin AE,Kremzer AA. Impaired phenotype of circulating endothelial microparticles in chronic heart failure patients:Relevance to body mass index[J]. Diabetes Metab Syndr,2015,9(4):230-236.
[2] Bootcov MR,Bauskin AR,Valenzuela SM,et al. MIC-1,a novel macrophage inhibitory cytokine,is a divergent member of the TGF-beta superfamily[J]. Proc Natl Acad Sci U S A,1997,94(21):11514-11519.
[3] Baek SJ,Kim JS,Nixon JB,et al. Expression of NAG-1,a transforming growth factor-beta superfamily member,by troglitazone requires the early growth response gene EGR-1[J]. J Biol Chem,2004,279(8):6883-6892.
[4] Lawton LN,Bonaldo MF,Jelenc PC,et al. Identification of a novel member of the TGF-beta super family highly expressed in human placenta[J]. Gene,1997,203(1):17-26.
[5]郭怀珠,郑瑞茂.脑干GDF15-GFRAL信号调控应激代谢反应[J].生理科学进展,2017,48(6):477.
[6]曹志刚,袁刚,向常清,等. 2型糖尿病患者血清生长分化因子-15的水平及其与大血管病变的关系[J].武汉大学学报(医学版),2012,33(4):498-502.
[7]刘玥明. 2型糖尿病患者血浆生长分化因子15水平与白蛋白尿及糖尿病视网膜病变关联性研究[D].上海:上海交通大学,2015.
[8]刘冬冬,梅岩艾.生长分化因子-15在神经系统、心血管疾病以及癌症进程中的作用[J].生理学报,2017,69(1):109-121.
[9] Kolodziejczyk SM,Hall BK. Signal transduction and TGF-βsuperfamily receptors[J]. Biochem Cell Biol,1996,74(3):299-314.
[10] Lakhal S,Talbot NP,Crosby A,et al. Regulation of growth differentiation factor-15 expression by intracellular iron[J].Blood,2009,113(7):1555-1563.
[11] Ilhan HD,Bilgin AB,Toylu A,et al. The expression of GDF-15 in the human vitreous in the presence of retinal pathologies with an inflammatory component[J]. Ocul Immunol Inflamm,2016,24(2):178-183.
[12]孟凡鹏.锌指基因ZFP580/ZNF580在GDF-15影响缺血再灌注后无复流中的作用及机制研究[D].石家庄:河北医科大学,2016.
[13]白帆,陆士娟.生长分化因子GDF-15与心血管疾病[J].中国热带医学,2012,12(5):633-636.
[14]杨曦,刘玉洁,马慧娟.生长分化因子15与肥胖及糖尿病[J].国际内分泌代谢杂志,2016,36(6):388-390.
[15] Schulz R,Kelm M,Heusch G. Nitric oxide in myocardial ischemia/reperfusion injury[J]. Cardiovasc Res,2004,61(3):402-413.
[16] Sharma A,Stevens SR,Lucas J,et al. Utility of growth differentiation factor-15,a marker of oxidative stress and inflammation,in chronic heart failure[J]. JACC Heart Fail,2017,5(10):724-734.
[17] Wallentin L,Hijazi Z,Andersson U,et al. Growth differentiation factor-15,a marker of oxidative stress and inflammation,for risk assessment in patients with atrial fibrillation:Insights from the apixaban for reduction in stroke and other thromboembolic events in atrial fibrillation trial[J]. Circulation,2014,130(21):1847-1858.
[18] Abulizi P,Loganathan N,Zhao D,et al. Growth differentiation factor-15 deficiency augments inflammatory response and exacerbates septic heart and renal injury induced by lipopolysaccharide[J]. Sci Rep,2017,7(1):1037.
[19] Mazagova M,Buikema H,van Buiten A,et al. Genetic deletion of growth differentiation factor-15 augments renal damage in both type 1 and type 2 models of diabetes[J]. Am J Physiol Renal Physiol,2013,305(9):1249-1264.
[20]尚盼盼,李亚蕊.生长分化因子-15水平变化与川崎病发病过程的相关性研究[J/CD].中华临床医师杂志(电子版),2017,11(2):213-216.
[21]刘云涛.不同水平糖耐量个体生长分化因子-15水平及相关性分析[J].广东医学,2012,33(2):297.
[22] Tsui KH,Hsu SY,Chung LC,et al. Growth differentiation factor-15:A p53 and demethylation upregulating gene represses cell proliferation,invasion,and tumorigenesis in bladder carcinoma cells[J]. Sci Rep,2015,5:12870.
[23] Potente M,Gerhardt H,Carmeliet P. Basic and therapeutic aspects of angiogenesis[J]. Cell,2011,146(6):873-887.
[24]尚小森,卫兵艳,刘田福,等.缺氧条件下GDF-15对心肌微血管内皮细胞成管的影响[J/CD].中西医结合心血管病电子杂志,2017,5(31):56-57.
[25]李博,吴慧颖,朴虎林,等.生长分化因子5对血管内皮细胞增殖和运动的影响[J].吉林大学学报(医学版),2011,37(6):1062-1064.
[26] Magnussen C,Blankenberg S. Biomarkers for heart failure:Small molecules with high clinical relevance[J]. J Intern Med,2018,283(6):530-543.
[27]阮园,王绍冠,王溢苏,等.血浆生长分化因子-15水平与2型糖尿病肾病分期的相关性研究[J].全科医学临床与教育,2018,16(2):137-140.
[28]王军,张松林,和旭梅,等.上调GDF-15表达对H2O2诱导的H9C2心肌细胞生物学特性及PI3K/AKT信号通路的影响[J].中国免疫学杂志,2018,34(5):658-664.
[29] Brown DA,Breit SN,Buring J,et al. Concentration in plasma of macrophage inhibitory cytokine-1 and risk of cardiovascular events in women:A nested case-control study[J]. Lancet,2002,359(9324):2159-6321.
[30] Arden GB,Sivaprasad S. Hypoxia and oxidative stress in the causation of diabetic retinopathy[J]. Curr Diabetes Rev,2011,7(5):291-304.
[31]刘玥明.患者血浆生长分化因子15水平与白蛋白尿及糖尿病视网膜病变关联性研究[D].上海:上海交通大学,2015.
[32] Macia L,Tsai WW,Nguyen AD,et al. Macrophage inhibitory cytokine 1(MIC-1/GDF15)decreases food intake,body weight and improves glucose tolerance in mice on normal&obesogenic diets[J]. PLoS One,2012,7(4):e34868.
[33]郭潮.血清生长分化因子-15与急性心肌梗死后左室重构程度的相关性研究[D].太原:山西医科大学,2013.
[34] Wollert KC,Kempf T,Wallentin L. Growth differentiation factor15 as a biomarker in cardiovascular disease[J]. Clin Chem,2017,63(1):140-151.
[35]贝雪艳,李军,曲忠慧,等.左心疾病相关性肺动脉高压患者血浆GDF-15 BNP的水平及意义[J].河北医学,2017,23(12):2025-2027.
[36] Kou H,Jin X,Gao D,et al. Association between growth differentiation factor 15 and left ventricular hypertrophy in hypertensive patients and healthy adults[J]. Clin Exp Hypertens,2018,40(1):8-15.
[37] Berezin AE,Kremzer AA. Impaired phenotype of circulating endothelial microparticles in chronic heart failure patients:Relevance to body mass index[J]. Diabetes Metab Syndr,2015,9(4):230-236.
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