on September 25, 2003
Published online before print September 25, 2003, doi: 10.1161/01.ATV.0000097282.22923.EF
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Submitted on August 22, 2003
Accepted on September 12, 2003
2
1 Integrin and Development of Atherosclerosis in a Mouse Model. Assessment of Risk
David G. Grenache ;
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.
* To whom correspondence should be addressed. E-mail: mary.zutter{at}vanderbilt.edu.
Objectives--The 
2
1 integrin serves as a collagen or collagen/laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the 21 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 21 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 21 integrin-deficient mouse to evaluate the contributions of the 21 integrin to the development of atherosclerosis.
Methods and Results--We generated wild-type (2+/+) or 21 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 21 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:
21integrincollagenatherosclerosisthrombosis
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