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Published on: July 3, 2018
Aberrant DNA methylation and miRNAs in coronary artery diseases and stroke: a systematic review
Insights
Epigenetic factors like DNA methylation and microRNA (miRNA) expression significantly influence cardiovascular diseases (CVDs), including coronary artery disease (CAD) and stroke. Understanding these epigenetic mechanisms is crucial for disease predisposition and treatment.
Area of Science:
- Cardiovascular Epigenetics
- Molecular Biology
- Genomics
Background:
- Coronary artery disease (CAD) and ischemic stroke are leading causes of cardiovascular diseases (CVDs).
- Epigenetic factors, particularly DNA methylation and microRNA (miRNA) expression, play a critical role in CVD development and progression.
- Understanding these epigenetic modifications is essential for identifying new therapeutic targets.
Purpose of the Study:
- To systematically review and synthesize current knowledge on the roles of DNA methylation and miRNAs in CAD and stroke.
- To highlight key epigenetic alterations and their associated biological pathways in these cardiovascular conditions.
Main Methods:
- Comprehensive literature search of PubMed, Science Direct, and Scopus databases.
- Systematic review of studies investigating DNA methylation and miRNA in CAD and stroke.
- Network analysis using ClueGO software and miRTargetLink database for pathway and gene interaction analysis.
Main Results:
- 32 studies on DNA methylation in CAD and stroke revealed alterations in global, genome-wide, and candidate loci methylation.
- Network analysis indicated that DNA methylation influences nitric oxide biosynthesis, homocysteine metabolism, and lipid storage.
- 83 studies identified 155 miRNAs associated with CAD and stroke, with specific miRNAs like mir-223 linked to cerebral infarction; common miRNAs targeted SP3 and SP1 genes.
Conclusions:
- Abnormal DNA methylation and miRNA expression are significantly implicated in the etiology and progression of CAD and stroke.
- Epigenetic dysregulation represents a key area for future research and potential therapeutic interventions in cardiovascular diseases.
- Further investigation into specific epigenetic mechanisms and their targets can lead to improved diagnostics and treatments for CAD and stroke.
Abstract:
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.
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