α₂β₁ Integrin and Development of Atherosclerosis in a Mouse Model: Assessment of Risk

Objectives - The α₂/β₁ integrin serves as a collagen or collagen/laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the α ₂/β₁ 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 α ₂/β₁ 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 α₂β₁ integrin-deficient mouse to evaluate the contributions of the α₂/β₁ integrin to the development of atherosclerosis. Methods and Results - We generated wild-type (α₂^+/+) or α₂/β₁ integrin-deficient (α₂^-/-) mice that were also deficient in the apolipoprotein E (ApoE) gene (ApoE^-/-) and compared atherosclerotic lesion development in α₂^+/+ ApoE^-/- and α₂^-/- 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 α 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 α₂/β₁ integrin expression is not attributable to enhanced development of atherosclerosis per se but may rather be a consequence of thrombotic complications at the plaques.