Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Newtown, Australia; Sydney Medical School, University of Sydney, Sydney, Australia.
School of Medical Sciences, University of Sydney, Sydney, Australia.
Heart Rhythm. 2018 Jan;15(1):137-144. doi: 10.1016/j.hrthm.2017.08.013. Epub 2017 Aug 18.
Inherited arrhythmia syndromes, including familial long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, and Brugada syndrome, can cause life-threatening arrhythmias and are responsible for a significant proportion of sudden deaths in the young. Identification of genetic mutations and pathophysiological changes that underlie disease development can inform clinical practice and guide novel drug development. However, disease mechanisms in a large number of patients remain elusive and pharmacologic treatment is suboptimal, so many patients rely on implantable cardioverter-defibrillator therapy. Induced pluripotent stem cell models of disease facilitate analysis of disease mechanisms in patient-specific cardiomyocytes, overcoming limitations of animal models and human tissue restrictions. This review outlines how studies using induced pluripotent stem cell-derived cardiomyocytes are contributing to our understanding of the mechanisms that underpin disease pathogenesis and their potential to facilitate new pharmacologic therapies and personalized medicine.
遗传性心律失常综合征，包括长 QT 综合征、儿茶酚胺多形性室性心动过速和 Brugada 综合征，可引起危及生命的心律失常，是年轻人猝死的重要原因。明确导致疾病发展的基因突变和病理生理变化可以为临床实践提供信息，并指导新型药物的开发。然而，大量患者的疾病机制仍不清楚，药物治疗效果也不佳，因此许多患者依赖植入式心脏复律除颤器治疗。疾病诱导多能干细胞模型有助于分析特定于患者的心肌细胞中的疾病机制，克服了动物模型和人体组织限制的不足。本综述概述了如何使用诱导多能干细胞衍生的心肌细胞来帮助我们理解疾病发病机制的机制，以及它们在促进新的药物治疗和个体化医学方面的潜力。
