Epigenetic mechanisms of vascular dysfunction in obesity and type 2 diabetes

Abstract

Over the last decade, several studies have shown that epigenetic modifications – defined as changes to the genome that do not alter the DNA sequence – may affect the expression of genes involved in inflammation, oxidative stress and angiogenesis. These alterations were recently shown to promote cardiovascular disease in the setting of obesity and type 2 diabetes. Most importantly, epigenetic modifications acquired during life may be transmitted to the next generations and may contribute to pathological cardiovascular traits already present during childhood. In the context of diabetes and obesity, high blood glucose levels and insulin resistance lead to modifications of the epigenome (DNA methylation, histone marks, noncoding RNAs), which may account for a persistent impairment of vascular and cardiac function, even after correction of underlying risk factors (intensive glycaemic control, weight loss). Hence, a careful assessment of the “epigenetic landscape” in cardiometabolic patients may contribute to the estimation of global cardiovascular risk, thus providing the tools for a personalised therapeutic approach. The present review describes the emerging role of epigenetics in the pathogenesis of cardiovascular complications in obesity and type 2 diabetes.