Global DNA methylation analysis of human atherosclerotic plaques reveals extensive genomic hypomethylation and reactivation at imprinted locus 14q32 involving induction of a miRNA cluster

Abstract

Significant changes in genomic methylation were identified in atherosclerotic lesions. The most prominent gene cluster activated via hypomethylation was detected at imprinted chromosomal locus 14q32 with several clustered miRNAs that were up-regulated. These results suggest that epigenetic changes are involved in atherogenesis and may offer new potential therapeutic targets for vascular diseases.

DNA Methylation Dynamics in Human Carotid Plaques After Cerebrovascular Events

“…[37][38][39] For example, the net CGI demethylation observed in coronary lesions of patients with myocardial infarction in our previous work, is consistent with the postrupture trend shown here. 37 The paucity of DNA methylation differences between symptomatic and asymptomatic carotid atheromas suggest that plaque rupture is associated with DNA methylation profiles that are either quantitatively weak or are specific for only in a minority of the cells populating the plaque.…”

Differential Promoter Methylation of Macrophage Genes Is Associated With Impaired Vascular Growth in Ischemic Muscles of Hyperlipidemic and Type 2 Diabetic Mice

“…9 DNA methylation is a well characterized mechanism of gene expression regulation as shown in cancer, aging, and other disorders, but the role of DNA methylation in other complex diseases like atherosclerosis and T2DM is incompletely understood. [10][11][12] Atherosclerotic lesions from human, mice, and rabbit models show significant hypomethylation and concomitant increase in transcriptional activity during atherogenesis. 12,13 Similarly, hypomethylation of extracellular superoxide dismutase was associated with the development of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.…”

“…[10][11][12] Atherosclerotic lesions from human, mice, and rabbit models show significant hypomethylation and concomitant increase in transcriptional activity during atherogenesis. 12,13 Similarly, hypomethylation of extracellular superoxide dismutase was associated with the development of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. 14 An atherogenic lipoprotein profile promotes DNA hypermethylation in Mϕs during the initiation and progression of atherosclerosis in ApoE -/-mice, suggesting cell-specific and tissue-specific epigenetic alterations in the presence of high-circulating lipids.…”

The Complex Cardiac Atherosclerotic Disorder: The Elusive Role of Genetics and the New Consensus of Systems Biology Approach

“…The epigenetics and the DNA methylation participate in many biological activities and in the atherosclerotic procedure [36]. Aavik et al [37] recognized in atherosclerotic plaques genomic hypomethylation that activated gene cluster in chromosomal locus 14q32 involving many clustered miRNAs that were up-regulated. The above authors concluded that epigenetic changes are implicated in the atherosclerotic process and provide novel potential therapeutic targets [37].…”