Experimental models of inherited cardiomyopathy and its therapeutics
Experimental models of inherited cardiomyopathy and its therapeutics
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DOI：
10.4330/wjc.v6.i12.1245
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发表时间：
2014-12-26
影响因子：
1.9
通讯作者：
Morimoto, Sachio
中科院分区：
文献类型：
--
作者：
Nonaka, Miki;Morimoto, Sachio
心肌病是一种主要的心肌疾病，分为肥厚型(HCM)、扩张型(DCM)和限制性心肌病(RCM)三种类型，最近被证明是一种单基因疾病，原因是心肌细胞表达的各种蛋白发生突变。HCM和RCM的突变通常会增加肌丝对胞浆钙离子的敏感性，导致收缩功能亢进和舒张期功能障碍。相反，DCM的突变通常会降低肌丝对胞浆钙离子和/或力量产生/传递的敏感性，导致收缩功能障碍。基因操作的转基因动物和敲入动物分别在其心脏内源性和外源性表达突变蛋白，为发现其发病的分子和细胞机制以及体内有前景的治疗策略提供了有价值的动物模型。最近，从患者S诱导的多能干细胞中分化出心肌细胞，作为遗传性心肌病的体外模型。在这篇综述中，我们概述了心肌病的实验模型，重点是揭示的分子和细胞致病机制和潜在的治疗方法。(C)2014百仕登出版集团有限公司，版权所有。
Cardiomyopathy is a disease of myocardium categorized into three major forms, hypertrophic (HCM), dilated (DCM) and restrictive cardiomyopathy (RCM), which has recently been demonstrated to be a monogenic disease due to mutations in various proteins expressed in cardiomyocytes. Mutations in HCM and RCM typically increase the myofilament sensitivity to cytoplasmic Ca2+, leading to systolic hyperfunction and diastolic dysfunction. In contrast, mutations in DCM typically decrease the myofilament sensitivity to cytoplasmic Ca2+ and/or force generation/transmission, leading to systolic dysfunction. Creation of genetically-manipulated transgenic and knock-in animals expressing mutant proteins exogenously and endogenously, respectively, in their hearts provides valuable animal models to discover the molecular and cellular mechanisms for pathogenesis and promising therapeutic strategy in vivo. Recently, cardiomyocytes have been differentiated from patient' s induced pluripotent stem cells as a model of inherited cardiomyopathies in vitro. In this review, we provide overview of experimental models of cardiomyopathies with a focus on revealed molecular and cellular pathogenic mechanisms and potential therapeutics. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.