Reduced Atherosclerotic Lesion Size in P-Selectin Deficient Apolipoprotein E-Knockout Mice Fed a Chow but Not a Fat Diet

Endothelial cells lining atherosclerotic, but not healthy sites, on human arteries express P-selectin. We investigated the role of P-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 of P-selectin deficiency, inducing atherosclerotic lesions via probably other adhesion molecules.