METTL3-dependent N 6 -methyladenosine RNA modification mediates the atherogenic inflammatory cascades in vascular endothelium

Significance Using in vitro and in vivo approaches, this report demonstrated the increased METTL3 expression and m 6 A hypermethylation in response to disturbed flow and oscillatory shear stress. METTL3 hypermethylates m 6 A sites at various downstream targets, up-regulates NLRP1 and down-regulates KLF4, and elicits atherogenic responses. Collectively, METTL3 and m 6 A hypermethylation epigenetically regulates the atherogenic gene expression and phenotypes in the initiation of atherosclerosis. Our data may enlighten the field of RNA epigenetics in the pathogenic mechanisms of heart diseases.