We show here that treatment with the PACAP agonist Maxadilan reduced the development of atherosclerosis in ApoE−/− mice, while M65 did not recapitulate the anti-atherogenic effects of PAC1 knockout, indicating that the latter is likely to be a result of developmental dysregulation unrelated to a potential therapeutic effect of PACAP acting at its cognate receptor, in treatment of atherosclerosis. This evidence concerns the gene APOE and atherosclerosis.