Dai Yao, Chen Danian, Xu Tingting
Department of Cardiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Pharmacol. 2022 Mar 3;13:815977. doi: 10.3389/fphar.2022.815977. eCollection 2022.
Atherosclerosis (AS) is a pathological process involving lipid oxidation, immune system activation, and endothelial dysfunction. The activated immune system could lead to inflammation and oxidative stress. Risk factors like aging and hyperhomocysteinemia also promote the progression of AS. Epigenetic modifications, including DNA methylation, histone modification, and non-coding RNA, are involved in the modulation of genes between the environment and AS formation. DNA methylation is one of the most important epigenetic mechanisms in the pathogenesis of AS. However, the relationship between the progression of AS and DNA methylation is not completely understood. This review will discuss the abnormal changes of DNA methylation in AS, including genome-wide hypermethylation dominating in AS with an increase of age, hypermethylation links with methyl supply and generating hyperhomocysteinemia, and the influence of oxidative stress with the demethylation process by interfering with the hydroxyl-methylation of TET proteins. The review will also summarize the current status of epigenetic treatment, which may provide new direction and potential therapeutic targets for AS.
动脉粥样硬化(AS)是一个涉及脂质氧化、免疫系统激活和内皮功能障碍的病理过程。激活的免疫系统会导致炎症和氧化应激。衰老和高同型半胱氨酸血症等危险因素也会促进AS的进展。表观遗传修饰,包括DNA甲基化、组蛋白修饰和非编码RNA,参与了环境与AS形成之间基因的调控。DNA甲基化是AS发病机制中最重要的表观遗传机制之一。然而,AS进展与DNA甲基化之间的关系尚未完全明确。本综述将讨论AS中DNA甲基化的异常变化,包括随着年龄增长在AS中占主导地位的全基因组高甲基化、与甲基供应相关的高甲基化以及通过干扰TET蛋白的羟甲基化而产生高同型半胱氨酸血症的情况,以及氧化应激对去甲基化过程的影响。本综述还将总结表观遗传治疗的现状,这可能为AS提供新的方向和潜在的治疗靶点。