Aberrant DNA methylation and miRNAs in coronary artery diseases and stroke: a systematic review

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. Highlights 1. 32 studies of DNA methylation on CAD and stroke were identified. 2. 155 miRNAs were associated with CAD, stroke and related phenotypes in 83 studies. 3. mir-223 hypomethylation and altered expression was associated with CVD subtypes.