The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
Tianjin Key Laboratory of Inflammatory Biology, Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Cells. 2022 Jul 30;11(15):2347. doi: 10.3390/cells11152347.
Cardiac fibrosis is a common pathophysiologic process associated with numerous cardiovascular diseases, resulting in cardiac dysfunction. Cardiac fibroblasts (CFs) play an important role in the production of the extracellular matrix and are the essential cell type in a quiescent state in a healthy heart. In response to diverse pathologic stress and environmental stress, resident CFs convert to activated fibroblasts, referred to as myofibroblasts, which produce more extracellular matrix, contributing to cardiac fibrosis. Although multiple molecular mechanisms are implicated in CFs activation and cardiac fibrosis, there is increasing evidence that epigenetic regulation plays a key role in this process. Epigenetics is a rapidly growing field in biology, and provides a modulated link between pathological stimuli and gene expression profiles, ultimately leading to corresponding pathological changes. Epigenetic modifications are mainly composed of three main categories: DNA methylation, histone modifications, and non-coding RNAs. This review focuses on recent advances regarding epigenetic regulation in cardiac fibrosis and highlights the effects of epigenetic modifications on CFs activation. Finally, we provide some perspectives and prospects for the study of epigenetic modifications and cardiac fibrosis.
心脏纤维化是一种与许多心血管疾病相关的常见病理生理过程,导致心脏功能障碍。心脏成纤维细胞(CFs)在细胞外基质的产生中发挥重要作用,是健康心脏中静止状态下的基本细胞类型。在应对多种病理应激和环境应激时,驻留的 CFs 转化为激活的成纤维细胞,即肌成纤维细胞,其产生更多的细胞外基质,导致心脏纤维化。尽管多种分子机制参与 CFs 的激活和心脏纤维化,但越来越多的证据表明表观遗传调控在这一过程中起着关键作用。表观遗传学是生物学中一个迅速发展的领域,为病理刺激和基因表达谱之间提供了一个调节链接,最终导致相应的病理变化。表观遗传修饰主要由三个主要类别组成:DNA 甲基化、组蛋白修饰和非编码 RNA。本综述重点关注心脏纤维化中表观遗传调控的最新进展,并强调了表观遗传修饰对 CFs 激活的影响。最后,我们为表观遗传修饰和心脏纤维化的研究提供了一些观点和展望。