Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), Utrecht, The Netherlands.
Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands.
Basic Res Cardiol. 2022 Apr 19;117(1):22. doi: 10.1007/s00395-022-00929-4.
Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by lethal arrhythmias and a risk to sudden cardiac death. A hallmark feature of AC is the progressive replacement of the ventricular myocardium with fibro-fatty tissue, which can act as an arrhythmogenic substrate further exacerbating cardiac dysfunction. Therefore, identifying the processes underlying this pathological remodelling would help understand AC pathogenesis and support the development of novel therapies. In this review, we summarize our knowledge on the different models designed to identify the cellular origin and molecular pathways underlying cardiac fibroblast and adipocyte cell differentiation in AC patients. We further outline future perspectives and how targeting the fibro-fatty remodelling process can contribute to novel AC therapeutics.
致心律失常性心肌病（AC）是一种遗传性疾病，其特征为致命性心律失常和心脏性猝死风险。AC 的一个显著特征是心室心肌逐渐被纤维脂肪组织取代，这可作为心律失常的基质，进一步加重心脏功能障碍。因此，确定导致这种病理性重塑的过程将有助于了解 AC 的发病机制并支持新型治疗方法的开发。在这篇综述中，我们总结了我们对不同模型的了解，这些模型旨在确定 AC 患者中心房成纤维细胞和脂肪细胞分化的细胞起源和分子途径。我们进一步概述了未来的展望以及靶向纤维脂肪重塑过程如何有助于新型 AC 治疗。
