Epigenetics of Cardiovascular Disease: A New ‘Beat' in Coronary Artery Disease

Abstract

Genome-wide association studies have become a powerful tool in the identification of disease-associated variants. Unfortunately, many of these studies have found that the estimated variability in cardiovascular disease (CVD) risk cannot be fully explained by traditional paradigms of genetic variation in protein-coding genes. Moreover, traditional views do not sufficiently explain the well-known link between CVD and environmental influence. We posit that epigenetics, defined as chromatin-based mechanisms important in the regulation of gene expression that do not involve changes in the DNA sequence per se, represents the missing link. The nuclear-based mechanisms that contribute to epigenetic gene regulation can be broadly separated into three unique but highly interrelated processes, namely DNA methylation and hydroxymethylation, histone density and post-translational modifications, and ribonucleic acid-based mechanisms. Together, they complement the cis/trans perspective on transcriptional control paradigms in blood vessels. Moreover, epigenetics provides a molecular basis for understanding how the environment influences the genome to modify CVD risk over the lifetime of a cell and its offspring. This review is an introduction to epigenetic function and CVD, with a focus on endothelial cell biology. Additionally, we highlight emerging concepts on epigenetic gene regulation that are highly relevant to atherosclerosis and coronary artery disease.

Epigenetic Regulation of Angiogenesis by JARID1B-Induced Repression of HOXA5

“…During endothelial dysfunction, these properties are lost and endothelial cells (ECs) promote vascular disease development. 1,2 Understanding the fundamental mechanisms governing endothelial phenotype switching offers novel approaches to prevent and alter the course of vascular disease. Epigenetic mechanisms conserve the cellular identity and give rise to developmental processes.…”

“…The epigenetic control of EC biology, however, is incompletely understood. [2][3][4] Histone methylation is an important mechanism of epigenetic regulation. Trimethylation at histone 3 lysine 4 (H3K4me3), located in promoter regions, is associated with gene expression.…”

Long noncoding RNA variations in cardiometabolic diseases

“…15 However, unlike the well-studied microRNAs, the knowledge on lncRNAs is still at a premature stage. 5,9,14 The lncRNAs are pervasively abundant and important for cells in every branch of organisms. They can be found in both the nucleus and cytoplasm.…”

“…2 Apart from the traditional and environmental risk factors for cardiometabolic diseases, including diabetes, dyslipidemia, hypertension and obesity, human genome variance is involved in the disease development. 5 To improve understanding of cardiometabolic disease pathogenesis, large efforts employing genome-wide association studies (GWAS) have identified numerous disease-associated singlenucleotide polymorphisms (SNPs). Most of them are enriched within noncoding elements, and very few of them are found in the coding that allows reasoning by the difference in structural change of the protein.…”

“…10,12,13 In contrast to the short ncRNAs that are highly conserved and their function primarily involved in post-transcriptional repression, lncRNAs are not well conserved and their functional mechanisms are diverse. 5,[13][14][15] In this review, we focus in particular on the role of recently discovered lncRNAs and their SNPs with respect to cardiometabolic diseases in humans.…”