Wnt信号通路在心血管疾病中的调控作用研究进展
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摘要
近年来Wnt信号通路与心血管疾病的研究越来越受重视,Wnt信号通路调控着心脏和血管的发育,在罹患心血管疾病时该通路会被再次激活从而发挥调控作用。本综述主要介绍Wnt信号通路的主要分类及其主要成员,以及各成员是如何参与到心血管疾病的发生、发展过程中的。本综述还简要介绍了众多成员为Wnt通路调控心血管疾病提供的许多有潜力的靶点,以及中药作用于这些靶点防治心血管疾病的进展及前景。
In recent years, more and more attention has been paid to the study of the Wnt signaling pathway and cardiovascular diseases. The Wnt signaling pathway regulates the development of the heart and blood vessels, and the pathway will be reactivated in the case of cardiovascular diseases and thus play a regulatory role. This review mainly introduces the main classification of Wnt signaling pathway and its main members, and how members are involved in the occurrence and development of cardiovascular diseases. This review also provides a brief introduction to many potential targets for the regulation of cardiovascular diseases by Wnt pathway and the prospects for the prevention and treatment of cardiovascular diseases by these targets.
In recent years, more and more attention has been paid to the study of the Wnt signaling pathway and cardiovascular diseases. The Wnt signaling pathway regulates the development of the heart and blood vessels, and the pathway will be reactivated in the case of cardiovascular diseases and thus play a regulatory role. This review mainly introduces the main classification of Wnt signaling pathway and its main members, and how members are involved in the occurrence and development of cardiovascular diseases. This review also provides a brief introduction to many potential targets for the regulation of cardiovascular diseases by Wnt pathway and the prospects for the prevention and treatment of cardiovascular diseases by these targets.
引文
[1]Nusse R,Brown A,Papkoff J,et al.A new nomenclature for int-1 and related genes:the Wnt gene family[J].Cell,1991,64(2):231.
[2]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017》概要[J].中国循环杂志,2018,33(1):1-8.
[3]国家卫生和计划生育委员会.2016中国卫生和计划生育统计年鉴[J]北京:中国协和医科大学出版社,2017.
[4]李华垠,陶静,马依彤,等.FrzA基因转导干预对大鼠体外缺血缺氧心肌细胞Wnt信号通路相关分子表达及细胞凋亡的影响[J].山东医药,2016,56(33):8-10.
[5]Ho YS,Tsai WH,Lin FC,et al.Cardioprotective Actions of TGFβRI Inhibition Through Stimulating Autocrine/Paracrine of Survivin and Inhibiting Wntin-Cardiac Progenitors[J].Stem Cells,2016,34(2):445-455.
[6]陈靖.血浆Wnt5a与冠心病和骨质疏松的相关性研究[D].重庆:重庆医科大学,2017.
[7]Zhuang Y,Mao JQ,Yu M,et al.Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/beta-catenin signaling[J].Cell Biol Int,2016,40(2):121-130.
[8]Quasnichka H,Slater SC,Beeching CA,et al.Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21expression[J].Circ Res,2006,99(12):1329-1337.
[9]王记,陆玉琴,赵信科,等.Wnt/β-catenin信号在高糖诱导H9c2心肌细胞损伤与凋亡中的作用[J].临床与病理杂志,2016,36(12):1955-1960.
[10]Kaga S,Zhan L,Altaf E,et al.Glycogen synthase kinase-3beta/beta-catenin promotes angiogenic and antiapoptotic signaling through the induction of VEGF,Bcl-2 and survivin expression in rat ischemic preconditioned myocardium[J].J Mol Cell Cardiol,2006,40(1):138-147.
[11]Morishita Y,Kobayashi K,Klyachko E,et al.Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response[J].Sci Rep,2016,6:21705.
[12]林晓斐.《中国居民营养与慢性病状况报告(2015年)》发布[J].中医药管理杂志,2015,23(13):89.
[13]尹春燕,肖延风.代谢及炎性因子在肥胖儿童高血压中的作用[J].中国妇幼健康研究,2017,28(12):1545-1547.
[14]刘玉苓,裴丽娜,都健,等.健康体检人群血清Wnt5a水平与腹型肥胖相关性的研究[J].中国糖尿病杂志,2014,22(7):622-624.
[15]谢永进.AngⅡ、醛固酮致心肌纤维化及Wnt1在其中的作用[D].北京:中国人民解放军医学院,2014.
[16]黄小芳,张韬,华玥,等.Wnt/β-连环蛋白在高糖诱导心肌成纤维细胞增殖中的作用[J].贵阳医学院学报,2014,39(1):30-34.
[17]Zhang M,Hagenmueller M,Riffel JH,et al.Calcium/calmodulin-dependent protein kinaseⅡcouples Wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardio-myopathy[J].Hypertension,2015,65(2):35-44.
[18]Lin H,Angeli M,Chung KJ.s FRP2 activates Wnt/β-catenin signaling in cardiac fibroblasts:differential roles in cell growth,energy metabolism,and extracellular matrix remodeling[J].Am J Physiol Cell Physiol,2016,311(5):C710-C719.
[19]周珊珊.Wnt-5a/Frizzled-2途径对心肌缺血再灌注损伤后心肌Ca2+变化的影响的研究[D].广州:南方医科大学,2011.
[20]吴翔.白藜芦醇后处理对缺氧/复氧H9C2心肌细胞钙超载的保护效应及作用机制研究[D].广州:南方医科大学,2015.
[21]李上海,梁伟钧,张亚娟,等.β结合素与大鼠心肌缺血再灌注损伤的作用机制[J].心脑血管病防治,2014,14(3):192-194,197.
[22]Barandon L,Casassus F,Leroux L,et al.Secreted frizzled-related protein-1 improves postinfarction scar formation through a modulation of inflammatory response[J].Arterioscler Thromb Vasc Biol,2011,31(11):e80-e87.
[23]Haq S,Michael A,Andreucci M,et al.Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth[J].Proc Natl Acad Sci U SA,2003,100(8):4610-4615.
[24]丁学亮,朱烨静,尹新华,等.Wnt信号通路在心肌肥厚中作用的研究进展[J].心脏杂志,2012,24(3):411-415.
[25]韩路拓,刘建勋,杨佳妹,等.心肌成纤维细胞Wnt信号通路在高糖环境下的调控变化[J].成都中医药大学学报,2017,40(4):23-26,127.
[26]尹茂山.SIRT1/Wnt/β-catenin信号通路在糖尿病心肌病发生发展过程中的变化及奥美沙坦酯的干预作用研究[D].济南:济南大学,2016.
[27]邱丽满.基于Wnt/β-catenin信号通路探讨黄芩苷在心肌细胞氧化损伤中的保护机制[D].福州:福建中医药大学,2017.
[28]韩路拓.活血化瘀方有效成分对高糖培养的心肌成纤维细胞Wnt信号通路的影响[D].北京:北京中医药大学,2014.
[29]王国钦,金伟,漆满英,等.稳心颗粒对大鼠心肌肥厚的影响及作用机制研究[J].中西医结合心脑血管病杂志,2011,9(4):462-463.
[2]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2017》概要[J].中国循环杂志,2018,33(1):1-8.
[3]国家卫生和计划生育委员会.2016中国卫生和计划生育统计年鉴[J]北京:中国协和医科大学出版社,2017.
[4]李华垠,陶静,马依彤,等.FrzA基因转导干预对大鼠体外缺血缺氧心肌细胞Wnt信号通路相关分子表达及细胞凋亡的影响[J].山东医药,2016,56(33):8-10.
[5]Ho YS,Tsai WH,Lin FC,et al.Cardioprotective Actions of TGFβRI Inhibition Through Stimulating Autocrine/Paracrine of Survivin and Inhibiting Wntin-Cardiac Progenitors[J].Stem Cells,2016,34(2):445-455.
[6]陈靖.血浆Wnt5a与冠心病和骨质疏松的相关性研究[D].重庆:重庆医科大学,2017.
[7]Zhuang Y,Mao JQ,Yu M,et al.Hyperlipidemia induces vascular smooth muscle cell proliferation involving Wnt/beta-catenin signaling[J].Cell Biol Int,2016,40(2):121-130.
[8]Quasnichka H,Slater SC,Beeching CA,et al.Regulation of smooth muscle cell proliferation by beta-catenin/T-cell factor signaling involves modulation of cyclin D1 and p21expression[J].Circ Res,2006,99(12):1329-1337.
[9]王记,陆玉琴,赵信科,等.Wnt/β-catenin信号在高糖诱导H9c2心肌细胞损伤与凋亡中的作用[J].临床与病理杂志,2016,36(12):1955-1960.
[10]Kaga S,Zhan L,Altaf E,et al.Glycogen synthase kinase-3beta/beta-catenin promotes angiogenic and antiapoptotic signaling through the induction of VEGF,Bcl-2 and survivin expression in rat ischemic preconditioned myocardium[J].J Mol Cell Cardiol,2006,40(1):138-147.
[11]Morishita Y,Kobayashi K,Klyachko E,et al.Wnt11 Gene Therapy with Adeno-associated Virus 9 Improves Recovery from Myocardial Infarction by Modulating the Inflammatory Response[J].Sci Rep,2016,6:21705.
[12]林晓斐.《中国居民营养与慢性病状况报告(2015年)》发布[J].中医药管理杂志,2015,23(13):89.
[13]尹春燕,肖延风.代谢及炎性因子在肥胖儿童高血压中的作用[J].中国妇幼健康研究,2017,28(12):1545-1547.
[14]刘玉苓,裴丽娜,都健,等.健康体检人群血清Wnt5a水平与腹型肥胖相关性的研究[J].中国糖尿病杂志,2014,22(7):622-624.
[15]谢永进.AngⅡ、醛固酮致心肌纤维化及Wnt1在其中的作用[D].北京:中国人民解放军医学院,2014.
[16]黄小芳,张韬,华玥,等.Wnt/β-连环蛋白在高糖诱导心肌成纤维细胞增殖中的作用[J].贵阳医学院学报,2014,39(1):30-34.
[17]Zhang M,Hagenmueller M,Riffel JH,et al.Calcium/calmodulin-dependent protein kinaseⅡcouples Wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardio-myopathy[J].Hypertension,2015,65(2):35-44.
[18]Lin H,Angeli M,Chung KJ.s FRP2 activates Wnt/β-catenin signaling in cardiac fibroblasts:differential roles in cell growth,energy metabolism,and extracellular matrix remodeling[J].Am J Physiol Cell Physiol,2016,311(5):C710-C719.
[19]周珊珊.Wnt-5a/Frizzled-2途径对心肌缺血再灌注损伤后心肌Ca2+变化的影响的研究[D].广州:南方医科大学,2011.
[20]吴翔.白藜芦醇后处理对缺氧/复氧H9C2心肌细胞钙超载的保护效应及作用机制研究[D].广州:南方医科大学,2015.
[21]李上海,梁伟钧,张亚娟,等.β结合素与大鼠心肌缺血再灌注损伤的作用机制[J].心脑血管病防治,2014,14(3):192-194,197.
[22]Barandon L,Casassus F,Leroux L,et al.Secreted frizzled-related protein-1 improves postinfarction scar formation through a modulation of inflammatory response[J].Arterioscler Thromb Vasc Biol,2011,31(11):e80-e87.
[23]Haq S,Michael A,Andreucci M,et al.Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth[J].Proc Natl Acad Sci U SA,2003,100(8):4610-4615.
[24]丁学亮,朱烨静,尹新华,等.Wnt信号通路在心肌肥厚中作用的研究进展[J].心脏杂志,2012,24(3):411-415.
[25]韩路拓,刘建勋,杨佳妹,等.心肌成纤维细胞Wnt信号通路在高糖环境下的调控变化[J].成都中医药大学学报,2017,40(4):23-26,127.
[26]尹茂山.SIRT1/Wnt/β-catenin信号通路在糖尿病心肌病发生发展过程中的变化及奥美沙坦酯的干预作用研究[D].济南:济南大学,2016.
[27]邱丽满.基于Wnt/β-catenin信号通路探讨黄芩苷在心肌细胞氧化损伤中的保护机制[D].福州:福建中医药大学,2017.
[28]韩路拓.活血化瘀方有效成分对高糖培养的心肌成纤维细胞Wnt信号通路的影响[D].北京:北京中医药大学,2014.
[29]王国钦,金伟,漆满英,等.稳心颗粒对大鼠心肌肥厚的影响及作用机制研究[J].中西医结合心脑血管病杂志,2011,9(4):462-463.
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