APOE and atherosclerosis: We validated our in vitro observations by imposing low shear stress in murine carotid arteries using the partial ligation model that promotes arterial wall remodeling and atherosclerosis in hypercholesterolemic mice.25 It should be noted that low shear stress is not sufficient to drive vascular inflammation per se, but it primes ECs for enhanced responses to inflammatory stimuli.6 Because atherosclerosis is a lipid-driven disease, we analyzed the function of HIF1α in partially ligated carotid arteries using hypercholesterolemic mice (ApoE−/− mice exposed to a high-fat diet for 6 weeks).