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. METHODS AND 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.
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. METHODS AND 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.
Authors: Li Zhu; Timothy J Stalker; Karen P Fong; Hong Jiang; Anh Tran; Irene Crichton; Eric K Lee; Keith B Neeves; Sean F Maloney; Hitoshi Kikutani; Atsushi Kumanogoh; Ellen Pure; Scott L Diamond; Lawrence F Brass Journal: Arterioscler Thromb Vasc Biol Date: 2009-04-23 Impact factor: 8.311
Authors: Amy L Pyle; James B Atkinson; Ambra Pozzi; Jeff Reese; Beate Eckes; Jeffrey M Davidson; Dan L Crimmins; Pampee P Young Journal: Am J Pathol Date: 2008-10-02 Impact factor: 4.307
Authors: Mari Levula; Niku Oksala; Nina Airla; Rainer Zeitlin; Juha-Pekka Salenius; Otso Järvinen; Maarit Venermo; Teemu Partio; Jukka Saarinen; Taija Somppi; VeliPekka Suominen; Jyrki Virkkunen; Juha Hautalahti; Reijo Laaksonen; Mika Kähönen; Ari Mennander; Leena Kytömäki; Juhani T Soini; Jyrki Parkkinen; Markku Pelto-Huikko; Terho Lehtimäki Journal: PLoS One Date: 2012-04-11 Impact factor: 3.240