Abstract 365: Increased Plasma Cholesterol Esterification by Lecithin-Cholesterol Acyltransferase Prevents Dysfunction of Red Blood Cells and Platelets and Protects from Development of Diet-Induced Atherosclerosis
Introduction Free cholesterol plays a vital role in maintaining cell membrane fluidity and function. Elevated levels of cholesterol in red blood cells (RBC) and platelets have been demonstrated to impair the function of these cells. In circulation, free cholesterol freely exchanges between cells and lipoproteins and lecithin-cholesterol acyltransferase (LCAT) plays a role in this exchange. The esterification of cholesterol by LCAT sequesters it in the interior of lipoprotein particles and thereby limits its movement between lipoproteins and cells. Previously, SR-B1 KO mice have been shown to have dysfunctional RBCs and platelets and this dysfunction is exacerbated by a high fat diet. These mice have a partial defect in cholesterol esterification and are susceptible to diet induced atherosclerosis.
Hypothesis We assessed in SR-BI KO mice whether increased cholesterol esterification by LCAT would improve numbers of RBCs and platelets, as well as prevent the development of atherosclerosis.
Methods and Results Control (C57BL/6), SR-B1 KO, SR-B1 KO x LCAT KO(DKO), and SR-B1 KO x LCAT-Trg(LCAT-Trg) mice were maintained on a western diet for 7 months. As previously observed, SR-B1 KO mice had decrease numbers of RBCs and platelets compared to control mice, and over expression of LCAT restored levels to that of wild type mice, while loss of LCAT further abrogated the decrease in cell counts(n=10). Unexpectedly, LCAT-Trg mice has the highest levels of cholesterol in plasma, but RBC and platelets showed the lowest levels of free cholesterol, as assessed by filipin staining. Atherosclerosis in western diet fed mice was assessed by Oil Red O in two ways by looking at the aortic root(n=4) and by en face analysis of the aorta(n=10). In the aortic root SRB-1KO and DKO mice showed 3x the amount of lesion size as controls, while LCAT-Trg mice had levels comparable to the controls mice. The en face analysis also showed that DKO mice had 3x the amount of lesions, while LCAT-Trg and SRB-1KO mice had levels comparable to control mice.
Conclusion LCAT is able to modulate the movement of cholesterol between circulating cells and lipoproteins thereby protecting RBCs and platelets. Our results further demonstrate a possible benefit of LCAT on the progression of atherosclerosis.
- © 2013 by American Heart Association, Inc.