Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of disease
Arrhythmogenic right ventricular cardiomyopathy: new insights into mechanisms of disease
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DOI：
10.1016/j.carpath.2009.10.006
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发表时间：
2010-05-01
影响因子：
3.7
通讯作者：
Huang, Hayden
中科院分区：
文献类型：
--
作者：
Saffitz, Jeffrey E.;Asimaki, Angeliki;Huang, Hayden
致心律失常性右室心肌病是一种以早期发生心律失常为特征的原发性心肌病，常与结构重构和收缩紊乱的程度不成比例。大约40%的致心律失常性右室心肌病患者在桥粒中有一个或多个编码蛋白的基因突变，桥粒是一种细胞间黏附连接，在心肌细胞中位于间盘内。一些桥粒蛋白既可以作为细胞黏附连接的结构蛋白，也可以作为Wnt配体介导的信号分子。越来越多的证据表明，桥粒蛋白的突变可以扰乱连接和胞浆中关键蛋白的正常平衡，这反过来又可以通过绕过正常的Wnt信号通路来改变基因表达。本文综述了致心律失常性右室心肌病发病机制的最新研究进展，并提出证据表明，该疾病是由细胞生物力学行为改变和信号改变共同引起的。(C)2010年，由爱思唯尔公司出版。
Arrhythmogenic right ventricular cardiomyopathy is a primary heart muscle disorder characterized by the early occurrence of arrhythmias often out of proportion to the extent of structural remodeling and contractile derangement. Approximately 40% of patients with arrhythmogenic right ventricular cardiomyopathy have one or more mutations in genes encoding proteins in desmosomes, intercellular adhesion junctions which, in cardiac myocytes, reside within intercalated disks. Some desmosomal proteins fulfill roles both as structural proteins in cell cell adhesion junctions and as signaling molecules in pathways mediated by Wnt ligands. Evidence is increasing that mutations in desmosomal proteins can perturb the normal balance of critical proteins in junctions and the cytosol which, in turn, could alter gene expression by circumventing normal Wnt signaling pathways. This review highlights recent advances in understanding the pathogenesis of arrhythmogenic right ventricular cardiomyopathy and presents evidence suggesting that the disease is caused by a combination of altered cellular biomechanical behavior and altered signaling. (C) 2010 Published by Elsevier Inc.