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

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.