Arrhythmogenic Right Ventricular Cardiomyopathy: New Insights Into Disease Mechanisms and Diagnosis
Arrhythmogenic Right Ventricular Cardiomyopathy: New Insights Into Disease Mechanisms and Diagnosis
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DOI：
10.2310/jim.0b013e3181c5e631
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发表时间：
2009-12-01
影响因子：
2.6
通讯作者：
Huang, Hayden
中科院分区：
文献类型：
--
作者：
Saffitz, Jeffrey E.;Asimaki, Angeliki;Huang, Hayden
致心律失常性右心室心肌病（ARVC）是一种原发性心肌疾病，其特征是早期发生严重的快速性心律失常，其程度往往与结构改变和收缩紊乱不成比例。大约40%的ARVC患者在编码桥粒蛋白质的基因中有一个或多个突变，桥粒是心肌细胞中位于闰盘内的细胞间粘附连接。一些桥粒蛋白既作为细胞间粘附连接的结构蛋白又作为核信号分子。已经提出，与ARVC有关的桥粒蛋白的突变可能扰乱连接和细胞质中蛋白质的正常平衡，这反过来又可能促进基因表达失调，从而绕过Writ信号传导途径的正常控制。本文综述了ARVC发病机制的最新进展，并提出了证据，表明该疾病是由改变的细胞生物力学行为和改变的信号传导相结合引起的。
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a primary heart muscle disorder characterized by the early occurrence of serious tachyarrhythmias often out of proportion to the extent of structural changes and contractile derangement. Approximately 40% of patients with ARVC 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 nuclear signaling molecules. It has been proposed that mutations in desmosomal proteins implicated in ARVC may perturb the normal balance of protein in junctions and the cytosol which, in turn, could promote dysregulated gene expression circumventing the normal controls of Writ signaling pathways. This review highlights recent advances in understanding the pathogenesis of ARVC and presents evidence, suggesting that the disease is caused by a combination of altered cellular biomechanical behavior and altered signaling.