Pathogenesis of Arrhythmogenic Cardiomyopathy.
Pathogenesis of Arrhythmogenic Cardiomyopathy.
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DOI：
10.1016/j.cjca.2015.04.012
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Saffitz JE
中科院分区：
文献类型：
--
作者：
Asimaki A;Kleber AG;Saffitz JE
致心律失常性心肌病(ACM)是一种原发心肌疾病。它的特点是频发室性心律失常和心源性猝死风险增加，通常出现在重大心肌重塑开始之前的早期表现。心肌变性，通常局限于右心室游离壁，代之以纤维脂肪瘢痕组织，在许多患者中发生。ACM是一种家族性疾病，但遗传外显率低，疾病表现高度可变。炎症可能会促进疾病的发展。运动似乎还会增加疾病的外显性，并加速疾病的发展。超过60%的先证者存在桥粒蛋白编码基因的突变，这增加了细胞-细胞黏附缺陷在疾病发病机制中发挥作用的可能性。最近的进展表明，经典的Wnt/β-连环蛋白和河马信号通路的改变，以及在将离子通道和其他蛋白质转运到心肌细胞的间盘方面存在缺陷。本文综述了目前对ACM发病机制的认识，并指出了今后的研究方向。
Arrhythmogenic cardiomyopathy (ACM) is a primary myocardial disease. It is characterized by frequent ventricular arrhythmias and increased risk of sudden cardiac death typically arising as an early manifestation before the onset of significant myocardial remodeling. Myocardial degeneration, often confined to the right ventricular free wall, with replacement by fibrofatty scar tissue, develops in many patients. ACM is a familial disease but genetic penetrance can be low and disease expression is highly variable. Inflammation may promote disease progression. It also appears that exercise increases disease penetrance and accelerates its development. More than 60% of probands harbor mutations in genes encoding desmosomal proteins, which has raised the possibility that defective cell-cell adhesion may play a role in disease pathogenesis. Recent advances have implicated changes in the canonical Wnt/β-catenin and Hippo signaling pathways and defects in forwarding trafficking of ion channels and other proteins to the intercalated disk in cardiac myocytes. This review summarizes current understanding of the pathogenesis of ACM and highlights future research directions.