Coronary artery disease (CAD) and ischemic stroke are the two most predominant forms of cardiovascular diseases (CVDs) caused by genetic, epigenetic and environmental risk factors. Although studies on the impact of 'epigenetics' in CVDs is not new, its effects are increasingly being realized as a key regulatory determinant that may drive predisposition, pathophysiology and therapeutic outcome. The most widely studied epigenetic risk factors are regulated by DNA methylation and miRNA expression. To keep pace with growing developments and discoveries, a comprehensive review was performed using Pubmed, Science Direct and Scopus databases to highlight the role of DNA methylation and miRNAs in CAD and stroke subjects. Network analysis was performed using ClueGO software and miRTargetLink database. We identified 32 studies of DNA methylation on CAD and stroke, of which, 6 studies showed differences in global DNA methylation, 10 studies reported the genome-wide difference in DNA methylation and 16 studies demonstrated altered DNA methylation at 14 candidate loci. The network analysis showed positive regulation of nitric oxide biosynthetic process, homocysteine metabolic process and negative regulation of lipid storage. About, 155 miRNAs were associated with CAD, stroke and related phenotypes in 83 studies. Interestingly, mir-223 hypomethylation and altered expression were associated with cerebral infarction and stroke. The target prediction for 18 common miRNAs between CAD and stroke showed strong interaction with SP3 and SP1 genes. This systematic review addresses the present knowledge on DNA methylation and miRNAs in CAD and stroke, whose abnormal regulation has been implicated in etiology or progression of the diseases.

中文翻译：

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冠状动脉疾病和中风中的异常 DNA 甲基化和 miRNA：系统评价。

冠状动脉疾病 (CAD) 和缺血性中风是由遗传、表观遗传和环境风险因素引起的两种最主要的心血管疾病 (CVD)。尽管关于“表观遗传学”在 CVD 中的影响的研究并不新鲜，但其影响正日益成为可能推动易感性、病理生理学和治疗结果的关键调控决定因素。研究最广泛的表观遗传风险因素受 DNA 甲基化和 miRNA 表达的调控。为了跟上不断增长的发展和发现，使用 Pubmed、Science Direct 和 Scopus 数据库进行了全面审查，以突出 DNA 甲基化和 miRNA 在 CAD 和中风受试者中的作用。使用 ClueGO 软件和 miRTargetLink 数据库进行网络分析。我们确定了 32 项关于 CAD 和中风的 DNA 甲基化研究，其中 6 项研究显示整体 DNA 甲基化存在差异，10 项研究报告了 DNA 甲基化的全基因组差异，16 项研究表明 14 个候选位点的 DNA 甲基化发生改变。网络分析显示一氧化氮生物合成过程、同型半胱氨酸代谢过程的正调控和脂质储存的负调控。在 83 项研究中，大约有 155 种 miRNA 与 CAD、中风和相关表型相关。有趣的是，mir-223 低甲基化和表达改变与脑梗塞和中风有关。CAD 和中风之间 18 种常见 miRNA 的目标预测显示与 SP3 和 SP1 基因有很强的相互作用。这篇系统综述解决了目前关于 CAD 和中风中 DNA 甲基化和 miRNA 的知识，