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Atherosclerosis. 2009 Aug;205(2):427-32. doi: 10.1016/j.atherosclerosis.2009.01.018. Epub 2009 Jan 23.

Atherosclerosis proceeds independently of thrombin-induced platelet activation in ApoE-/- mice.

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  • 1Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia. Justin.Hamilton@med.monash.edu.au


Platelet activation has long been postulated to contribute to the development of atherosclerotic plaques, although the mechanism by which this might occur remains unknown. Thrombin is a potent platelet activator and transfusion of thrombin-activated platelets into mice increases plaque formation, suggesting that thrombin-induced platelet activation might contribute to platelet-dependent atherosclerosis. Platelets from protease-activated receptor 4-deficient (Par4-/-) mice fail to respond to thrombin. To determine whether thrombin-activated platelets play a necessary role in a model of atherogenesis, we compared plaque formation and progression in Par4+/+ and Par4-/- mice in the atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) background. Littermate Par4+/+ and Par4-/- mice, all ApoE-/-, were placed on a Western diet (21% fat, 0.15% cholesterol) for 5 or 10 weeks. The percent of aortic lumenal surface covered by plaques in Par4+/+ and Par4-/- mice was not different at either time point (2.2+/-0.3% vs. 2.5+/-0.2% and 5.1+/-0.4% vs. 5.6+/-0.4% after 5 and 10 weeks, respectively). Further, no differences were detected in the cross-sectional area of plaques measured at the aortic root (1.53+/-0.17 vs. 1.66+/-0.16x10(5)microm(2) and 12.56+/-1.23 vs. 13.03+/-0.55x10(5)microm(2) after 5 and 10 weeks, respectively). These findings indicate that thrombin-mediated platelet activation is not required for the early development of atherosclerotic plaques in the ApoE-/- mouse model and suggest that, if platelet activation is required for plaque formation under these experimental conditions, platelet activators other than thrombin suffice.

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