Reduced Atherosclerotic Lesion Size in <i>P</i>‐Selectin Deficient Apolipoprotein <i>E</i>‐Knockout Mice Fed a Chow but Not a Fat Diet

Abstract

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 &lt; .03) , 6 ( P &lt; .001), and 15 ( P &lt; .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.