m6A甲基化修饰在心血管疾病中的调控作用及机制

Regulatory Effects and Mechanisms of m6A Methylation Modification in Cardiovascular Diseases

N6-甲基腺嘌呤(N6-methyladenosine,m6A)是真核生物mRNA中最普遍的内部化学修饰。研究表明,m6A甲基化在心力衰竭、心肌肥厚、动脉粥样硬化、缺血性心肌病等心血管疾病中发挥着重要的调控作用。如m6A甲基转移酶可延缓心力衰竭并促进心力衰竭后的心肌修复,为心力衰竭的治疗提供新的视角;各类m6A甲基化调节因子可通过调节内皮细胞功能、炎症反应和细胞周期进程,从而抑制动脉粥样硬化的进程;在缺血性心肌病中,m6A甲基化转移酶与去甲基化酶通过反馈调节机制为缺血性心肌病的治疗奠定基础。此外,新近的研究表明,mRNA的表观遗传修饰对心肌肥厚有很大的影响,同时研究人员在表观遗传修饰调节心肌肥厚分子机制的研究中取得了重大进展,发现m6A甲基化通过调节相关信号通路可作为维持心脏功能与稳态的治疗靶点。鉴于此,该文通过综述近三年国内外最新研究进展,深入探讨了m6A甲基化在各类心血管疾病中的调控作用及其分子机制,旨在为各类心血管疾病的防治提供理论参考。

m6A (N6-methyladenine) is the most common internal chemical modification in eukaryotic mRNA.Studies have shown that M6A methylation plays an important role in the regulation of cardiovascular diseases such as heart failure,myocardial hypertrophy,atherosclerosis and ischemic cardiomyopathy,and has made great progress in the past three years.For example,m6A methyltransferase can delay heart failure and promote myocardial repair after heart failure,which provides a new perspective for the treatment of heart failure;various m6A methylation regulators can inhibit the process of atherosclerosis by regulating endothelial cell function,inflammatory response and cell cycle progression.In ischemic cardiomyopathy,m6A methyltransferase and demethylase lay a foundation for the treatment of ischemic cardiomyopathy through feedback regulation.In addition,recent studies have shown that epigenetic modification of mRNA has a great effect on cardiac hypertrophy.At the same time,researchers have made great progress in the study of the molecular mechanism of epigenetic modification in the regulation of cardiac hypertrophy.It has been found that m6A methylation can be used as a therapeutic target for maintaining cardiac function and homeostasis by regulating related signal pathways.In view of this,by reviewing the latest research progress at home and abroad in the past three years,this paper deeply discussed the regulatory role and molecular mechanism of m6A methylation in various cardiovascular diseases,in order to provide theoretical reference for the prevention and treatment of various cardiovascular diseases.