BH4 supplementation has shown promise in preclinical models of atherosclerosis, inhibiting atherogenesis in apolipoprotein E knockout (ApoE-KO) mice fed a high-cholesterol diet [117], and reversing severe atherosclerosis in ApoE-KO mice with partial carotid ligation fed a high-fat diet [118]. This evidence concerns the gene APOE and atherosclerosis.