Critical roles of m6A methylation in cardiovascular diseases

Cardiovascular diseases (CVDs) have been established as a major cause of mortality globally. However, the exact pathogenesis remains obscure. N6-methyladenosine (m(6)A) methylation is the most common epigenetic modification on mRNAs regulated by methyltransferase complexes (writers), demethylase transferases (erasers) and binding proteins (readers). It is now understood that m(6)A is a major player in physiological and pathological cardiac processes. m(6)A methylation are potentially involved in many mechanisms, for instance, regulation of calcium homeostasis, endothelial function, different forms of cell death, autophagy, endoplasmic reticulum stress, macrophage response and inflammation. In this review, we will summarize the molecular functions of m(6)A enzymes. We mainly focus on m(6)A-associated mechanisms and functions in CVDs, especially in heart failure and ischemia heart disease. We will also discuss the potential application and clinical transformation of m(6)A modification.