Li Chia-Jung, Chen Chien-Sheng, Yiang Giou-Teng, Tsai Andy Po-Yi, Liao Wan-Ting, Wu Meng-Yu
Department of Obstetrics and Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan.
Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 231, Taiwan.
J Clin Med. 2019 Apr 16;8(4):520. doi: 10.3390/jcm8040520.
Cardiomyopathy is a group of heterogeneous cardiac diseases that impair systolic and diastolic function, and can induce chronic heart failure and sudden cardiac death. Cardiomyopathy is prevalent in the general population, with high morbidity and mortality rates, and contributes to nearly 20% of sudden cardiac deaths in younger individuals. Genetic mutations associated with cardiomyopathy play a key role in disease formation, especially the mutation of sarcomere encoding genes and ATP kinase genes, such as titin, lamin A/C, myosin heavy chain 7, and troponin T1. Pathogenesis of cardiomyopathy occurs by multiple complex steps involving several pathways, including the Ras-Raf-mitogen-activated protein kinase-extracellular signal-activated kinase pathway, G-protein signaling, mechanotransduction pathway, and protein kinase B/phosphoinositide 3-kinase signaling. Excess biomechanical stress induces apoptosis signaling in cardiomyocytes, leading to cell loss, which can induce myocardial fibrosis and remodeling. The clinical features and pathophysiology of cardiomyopathy are discussed. Although several basic and clinical studies have investigated the mechanism of cardiomyopathy, the detailed pathophysiology remains unclear. This review summarizes current concepts and focuses on the molecular mechanisms of cardiomyopathy, especially in the signaling from mutation to clinical phenotype, with the aim of informing the development of therapeutic interventions.
心肌病是一组异质性心脏疾病，会损害心脏的收缩和舒张功能，并可导致慢性心力衰竭和心源性猝死。心肌病在普通人群中普遍存在，发病率和死亡率都很高，在年轻个体的心源性猝死中占近20%。与心肌病相关的基因突变在疾病形成中起关键作用，尤其是肌节编码基因和ATP激酶基因的突变，如肌联蛋白、核纤层蛋白A/C、肌球蛋白重链7和肌钙蛋白T1。心肌病的发病机制通过涉及多个途径的多个复杂步骤发生，包括Ras-Raf-丝裂原活化蛋白激酶-细胞外信号调节激酶途径、G蛋白信号传导、机械转导途径和蛋白激酶B/磷脂酰肌醇3激酶信号传导。过度的生物力学应激会诱导心肌细胞凋亡信号，导致细胞丢失，进而可诱导心肌纤维化和重塑。本文讨论了心肌病的临床特征和病理生理学。尽管一些基础研究和临床研究已经对心肌病的机制进行了调查，但详细的病理生理学仍不清楚。本综述总结了当前的概念，并重点关注心肌病的分子机制，特别是从突变到临床表型的信号传导，旨在为治疗干预措施的开发提供信息。
