表观遗传修饰在蒽环类药物导致心脏毒性中的作用机制研究

Mechanism of epigenetic modification in anthracycline-induced cardiotoxicity

蒽环类药物如阿霉素(DOX)可用于多种癌症的治疗,但其引起的心脏毒性限制了其临床应用。了解阿霉素心脏毒性机制,对肿瘤心脏病学这一新兴领域的发展至关重要,如何预测、诊断和防治这种不良反应需引起高度重视和思考。由于DOX与线粒体功能障碍有关,以线粒体代谢物为底物的表观遗传修饰酶最有可能受到影响。文章对表观遗传修饰,即DNA甲基化、组蛋白修饰和非编码RNA表达进行综述,以了解DOX引起心脏毒性的表观遗传学机制。

Anthracyclines such as doxorubicin(DOX)are used in the treatment of various cancers,but their cardiotoxicity limits their clinical application.Understanding the mechanism of doxorubicin cardiotoxicity is crucial to the development of the emerging field of oncological cardiology.How to predict,diagnose and prevent this adverse reaction requires great attention and consideration.Since DOX is associated with mitochondrial dysfunction,epigenetic modifying enzymes that use mitochondrial metabolites as substrates are most likely to be affected.This article reviews epigenetic modifications,namely DNA methylation,histone modifications,and noncoding RNA expression,to understand the epigenetic mechanism of DOX-induced cardiotoxicity.