Department of Stem Cell Biology, Centre of Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Faculty of Medicine and Health Sciences, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK.
Trends Mol Med. 2019 Sep;25(9):775-790. doi: 10.1016/j.molmed.2019.06.005. Epub 2019 Jul 17.
Hypertrophic cardiomyopathy (HCM) is a prevalent and complex cardiovascular disease where cardiac dysfunction often associates with mutations in sarcomeric genes. Various models based on tissue explants, isolated cardiomyocytes, skinned myofibrils, and purified actin/myosin preparations have uncovered disease hallmarks, enabling the development of putative therapeutics, with some reaching clinical trials. Newly developed human pluripotent stem cell (hPSC)-based models could be complementary by overcoming some of the inconsistencies of earlier systems, whilst challenging and/or clarifying previous findings. In this article we compare recent progress in unveiling multiple HCM mechanisms in different models, highlighting similarities and discrepancies. We explore how insight is facilitating the design of new HCM therapeutics, including those that regulate metabolism, contraction and heart rhythm, providing a future perspective for treatment of HCM.
肥厚型心肌病（HCM）是一种常见且复杂的心血管疾病，心脏功能障碍通常与肌节基因的突变有关。基于组织外植体、分离的心肌细胞、去皮肌纤维和纯化的肌动球蛋白制剂的各种模型揭示了疾病特征，使潜在治疗药物的开发成为可能，其中一些已进入临床试验。新开发的基于人多能干细胞（hPSC）的模型可以通过克服早期系统的一些不一致性来提供补充，同时挑战和/或澄清以前的发现。在本文中，我们比较了不同模型中揭示多种 HCM 机制的最新进展，强调了相似点和差异点。我们探讨了如何洞察有助于设计新的 HCM 治疗药物，包括那些调节代谢、收缩和心律的药物，为 HCM 的治疗提供了未来的视角。
