School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Life Sci. 2021 Apr 15;271:119186. doi: 10.1016/j.lfs.2021.119186. Epub 2021 Feb 9.
Myocardial fibrosis (MF) is a reactive remodeling process in response to myocardial injury. It is mainly manifested by the proliferation of cardiac muscle fibroblasts and secreting extracellular matrix (ECM) proteins to replace damaged tissue. However, the excessive production and deposition of extracellular matrix, and the rising proportion of type I and type III collagen lead to pathological fibrotic remodeling, thereby facilitating the development of cardiac dysfunction and eventually causing heart failure with heightened mortality. Currently, the molecular mechanisms of MF are still not fully understood. With the development of epigenetics, it is found that epigenetics controls the transcription of pro-fibrotic genes in MF by DNA methylation, histone modification and noncoding RNAs. In this review, we summarize and discuss the research progress of the mechanisms underlying MF from the perspective of epigenetics, including the newest m6A modification and crosstalk between different epigenetics in MF. We also offer a succinct overview of promising molecules targeting epigenetic regulators, which may provide novel therapeutic strategies against MF.
心肌纤维化(MF)是心肌损伤后的一种反应性重塑过程。它主要表现为心肌成纤维细胞的增殖和分泌细胞外基质(ECM)蛋白来替代受损组织。然而,细胞外基质的过度产生和沉积,以及 I 型和 III 型胶原比例的上升,导致病理性纤维化重塑,从而促进了心脏功能障碍的发展,最终导致心力衰竭死亡率升高。目前,MF 的分子机制仍不完全清楚。随着表观遗传学的发展,人们发现表观遗传学通过 DNA 甲基化、组蛋白修饰和非编码 RNA 来控制 MF 中促纤维化基因的转录。在这篇综述中,我们从表观遗传学的角度总结和讨论了 MF 机制的研究进展,包括最新的 m6A 修饰和 MF 中不同表观遗传学之间的串扰。我们还简要概述了针对表观遗传调节剂的有前途的分子,这可能为 MF 的治疗提供新的策略。