title: Epigenetics of Cardiovascular Disease - A New "Beat" in Coronary Artery Disease.
abstract: Genome-wide association studies (GWAS) 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 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 cardiovascular disease 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 sequenceper 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: DNA methylation and hydroxymethylation; histone density and post-translational modifications; and RNA-based mechanisms. Together they complement thecis/transperspective on transcriptional control paradigms in blood vessels. Moreover, it provides a molecular basis for understanding how the environment impacts the genome to modify cardiovascular disease risk over the lifetime of a cell and its offspring. This review provides an introduction to epigenetic function and cardiovascular disease, 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.
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada ; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Turgeon
authors.affiliation: Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada ; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Aravin N
authors.initials: AN
authors.lastname: Sukumar
authors.affiliation: Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada ; Institute of Medical Sciences, University of Toronto, Toronto, ON, Canada ; Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute, St. Michael's Hospital, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Marsden
keywords: ANRIL; DNA methylation; cardiovascular disease; eNOS; endothelial cells; epigenetics; histone posttranslational modifications and density; long noncoding RNA