The disturbed flow-upregulated endothelial DNMT1 inhibits the expression of ALDH2, ALDH3A1, and ALDH6A1 through promoting their promoter methylation; dysregulation of ALDH2, ALDH3A1, and ALDH6A1 results in impairment in β-alanine, carnosine, and acetyl-CoA biosynthesis, leading to increased Smad2/3 phosphorylation and activation of the TGF-β signaling that ultimately causes EndoMT and atherosclerosis. The gene discussed is ALDH2; the disease is atherosclerosis.