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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:2104.)
© 2003 American Heart Association, Inc.

Thrombosis

₂ß₁ Integrin and Development of Atherosclerosis in a Mouse Model

Assessment of Risk

David G. Grenache; Trey Coleman; Clay F. Semenkovich; Samuel A. Santoro; Mary M. Zutter

From the Departments of Pathology & Immunology (D.G.G., S.A.S., M.M.Z.), Medicine (T.C., C.F.S.), and Cell Biology and Physiology (C.F.S.), Washington University School of Medicine, St Louis, Mo.

Correspondence to Mary M. Zutter, Department of Pathology, Vanderbilt University School of Medicine, C-3321A, 1161 21st Ave S, Nashville, TN 37232-2561. E-mail mary.zutter{at}vanderbilt.edu

Objectives— The ₂ß₁ integrin serves as a collagen or collagen/laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the ₂ß₁ integrin is a critical mediator of platelet adhesion to collagen. Epidemiologic studies suggest a direct correlation between the genetically determined platelet surface density of the ₂ß₁ integrin and the risk of thrombotic diseases, such as myocardial infarction and stroke, in the young, which are well-established complications of atherosclerosis. We have now used the ₂ß₁ integrin–deficient mouse to evaluate the contributions of the ₂ß₁ integrin to the development of atherosclerosis.

Methods and Results— We generated wild-type (₂^+/+) or ₂ß₁ integrin–deficient (₂^-/-) mice that were also deficient in the apolipoprotein E (ApoE) gene (ApoE^-/-) and compared atherosclerotic lesion development in ₂^+/+ ApoE^-/- and ₂^-/- ApoE^-/- mice that were fed a high-fat, cholesterol-containing diet for 6 or 15 weeks. Total lesional area did not differ significantly between the ₂-null animals and the wild-type animals at either 6 or 15 weeks.

Conclusions— Our results suggest that risk for arterial thrombotic disease associated with high-level ₂ß₁ integrin expression is not attributable to enhanced development of atherosclerosis per se but may rather be a consequence of thrombotic complications at the plaques.

Key Words: ₂ß₁ • integrin • collagen • atherosclerosis • thrombosis

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