Alpha2beta1 integrin and development of atherosclerosis in a mouse model: assessment of risk.
OBJECTIVE
The alpha2beta1 integrin serves as a collagen or collagen/laminin receptor on many cell types, including endothelial cells and platelets. Many studies indicate that the alpha2beta1 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 alpha2beta1 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 alpha2beta1 integrin-deficient mouse to evaluate the contributions of the alpha2beta1 integrin to the development of atherosclerosis.


RESULTS
We generated wild-type (alpha2+/+) or alpha2beta1 integrin-deficient (alpha2-/-) mice that were also deficient in the apolipoprotein E (ApoE) gene (ApoE-/-) and compared atherosclerotic lesion development in alpha2+/+ ApoE-/- and alpha2-/- 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 alpha2-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 alpha2beta1 integrin expression is not attributable to enhanced development of atherosclerosis per se but may rather be a consequence of thrombotic complications at the plaques.
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000378:metabolism; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005487:Foam Cells / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D038982:Integrin alpha2beta1 / Q000172:deficiency* / Q000378:metabolism*; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D012307:Risk Factors; D012850:Sinus of Valsalva / Q000378:metabolism / Q000473:pathology
D001057:Apolipoproteins E; D038982:Integrin alpha2beta1; D008074:Lipoproteins