Key Laboratory of Medical Electrophysiology, Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, China.
Cardiology, Angiology, Haemostaseology, and Medical Intensive Care, Medical Centre Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Stem Cell Rev Rep. 2023 Nov;19(8):2683-2708. doi: 10.1007/s12015-023-10615-0. Epub 2023 Sep 20.
Arrhythmogenic cardiomyopathy (ACM) is a hereditary myocardial disease characterized by the replacement of the ventricular myocardium with fibrous fatty deposits. ACM is usually inherited in an autosomal dominant pattern with variable penetrance and expressivity, which is mainly related to ventricular tachyarrhythmia and sudden cardiac death (SCD). Importantly, significant progress has been made in determining the genetic background of ACM due to the development of new techniques for genetic analysis. The exact molecular pathomechanism of ACM, however, is not completely clear and the genotype-phenotype correlations have not been fully elucidated, which are useful to predict the prognosis and treatment of ACM patients. Different gene-targeted and transgenic animal models, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) models, and heterologous expression systems have been developed. Here, this review aims to summarize preclinical ACM models and platforms promoting our understanding of the pathogenesis of ACM and assess their value in elucidating the ACM genotype-phenotype relationship.
致心律失常性心肌病（ACM）是一种遗传性心肌疾病，其特征是心室心肌被纤维脂肪沉积物取代。ACM 通常以常染色体显性遗传模式遗传，具有可变的外显率和表现度，主要与室性心动过速和心源性猝死（SCD）有关。重要的是，由于遗传分析新技术的发展，ACM 的遗传背景已取得显著进展。然而，ACM 的确切分子发病机制尚不完全清楚，基因型-表型相关性也未完全阐明，这有助于预测 ACM 患者的预后和治疗。已经开发了不同的基因靶向和转基因动物模型、人诱导多能干细胞衍生的心肌细胞（hiPSC-CM）模型和异源表达系统。在此，本综述旨在总结 ACM 的临床前模型和平台，以促进我们对 ACM 发病机制的理解，并评估它们在阐明 ACM 基因型-表型关系方面的价值。
