Epigenetics in Cardiovascular Disease

All three major classes of epigenetic processes-methylation, histone modification, and RNA-based mechanisms-are implicated in the pathogenesis of cardiovascular disease (CVD). Differential methylation of repetitive elements throughout the genome as well as specific regions has been associated with CVD-related traits such as inflammation, dyslipidemia, hypertension, and obesity. Although advances in array technology have enabled cost-effective epigenome-wide screens of DNA methylation in CVD, such studies have yet to produce widely used risk stratification tools or treatment approaches. Posttranslational modification of histone proteins has been show to contribute to a variety of cardiovascular phenotypes including atherosclerosis, inflammation, hypertension, diabetic cardiomyopathy, cardiac hypertrophy, stroke, heart failure, and abdominal aortic aneurysm; it has also been observed in context of common CVD drugs, namely, statins. A growing body of evidence supports the role of microRNAs in the development of myocardial infarction, angina pectoris, apoptosis, arrhythmias, and cardiac hypertrophy. Translation of epidemiologic and animal studies to clinical utility has been quite limited. Drugs that impact posttranslational modification of histone proteins have shown promise in the context of heart failure and myocardial injury, but have yet to be tested in human trials. MicroRNAs offer valuable potential as a diagnostic tool for acute coronary syndromes, but the development of microRNA-based CVD therapies is still in its infancy. The most promising epigenetic therapy for CVD to date, BET inhibitor RVX-208, has been evaluated in two trials of blood lipids, atherosclerosis, and major adverse cardiovascular events, yielding discrepant results. On the balance, epigenetics continues to show considerable potential to impact CVD risk stratification, diagnostics, and therapy but still faces a long road to successful clinical translation.