2 1 Integrin and Development of Atherosclerosis in a Mouse Model: Assessment of Risk

Objectives - The alpha(2)beta(1) integrin serves as a collagen or collagen/ laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the alpha(2)beta(1) 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 alpha(2)beta(1) 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 alpha(2)beta(1) integrin - deficient mouse to evaluate the contributions of the alpha(2)beta(1) integrin to the development of atherosclerosis. Methods and Results - We generated wild- type (alpha(2)(+/+)) or alpha(2)beta(1) integrin - deficient ( alpha(2)(-/-)) mice that were also deficient in the apolipoprotein E ( ApoE) gene ( ApoE (-/-)) and compared atherosclerotic lesion development in alpha(2)(+/+) ApoE (-/-) and alpha(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 alpha (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 alpha(2)beta(1) integrin expression is not attributable to enhanced development of atherosclerosis per se but may rather be a consequence of thrombotic complications at the plaques.