Epigenetic modifications of the renin–angiotensin system in cardiometabolic diseases

Abstract Cardiometabolic diseases (CMDs) are among the most prevalent and the highest mortality diseases. Single disease etiology such as gene mutation, polymorphisms, or environmental exposure has failed to explain the origin of CMD. This can be evident in the discrepancies in disease susceptibility among individuals exposed to the same environmental insult or who acquire the same genetic variation. Epigenetics is the intertwining of genetic and environmental factors that results in diversity in the disease course, severity, and prognosis among individuals. Environmental exposures modify the epigenome and thus provide a link for translating environmental impact on changes in gene expression and precipitation to pathological conditions. Renin–angiotensin system (RAS) is comprising genes responsible for the regulation of cardiovascular, metabolic, and glycemic functions. Epigenetic modifications of RAS genes can lead to overactivity of the system, increased sympathetic activity and autonomic dysfunction ultimately contributing to the development of CMD. In this review, we describe the three common epigenetic modulations targeting RAS components and their impact on the susceptibility to cardiometabolic dysfunction. Additionally, we highlight the therapeutic efforts of targeting these epigenetic imprints to the RAS and its effects.