Reduced Atherosclerotic Lesion Size inP-Selectin Deficient ApolipoproteinE-Knockout Mice Fed a Chow but Not a Fat Diet

Abstract

Endothelial cells lining atherosclerotic, but not healthy sites, on human arteries expressP-selectin. We investigated the role ofP-selectin on the development of vascular lesions in an ApoE−/−male mice. Double-knockout (ApoE−/−,P-selectin-/-; DKO) were compared to single-knockout (ApoE−/−; SKO) mice. They were fed a chow or fat diet for 3, 6, 15, and 20 weeks, without any differences in cholesterol levels. DKO mice fed a chow diet exhibited a ratio of lesion area over media lower than SKO mice, for 3 (P<.03) , 6 (P<.001), and 15 (P<.02) weeks. DKO mice fed a fat diet showed a lower ratio only at 3 weeks.P-selectin deficiency in ApoE−/−mice has a protective effect in atherosclerotic lesions development. Reduction of lesion size depends on diet type and duration. A fat diet could neutralize the beneficial effects ofP-selectin deficiency, inducing atherosclerotic lesions via probably other adhesion molecules.