Suppressing thrombin generation is compatible with the development of atherosclerosis in mice

Thrombosis Research
D J GraingerC D Byrne

Abstract

Thrombin has been proposed to play a key role in the development of atherosclerosis, both by promoting fibrin deposition into the atherosclerotic vessel wall and also by signalling through thrombin receptors. Unfortunately, mice homozygous for a deletion of the prothrombin gene (FII) die in utero, making a direct assessment of the role of thrombin during atherogenesis difficult. We have assessed the contribution of thrombin-dependent processes to vascular lipid lesion formation in the atherosclerosis-prone apolipoprotein E (ApoE)-deficient mice by inhibiting thrombin generation with warfarin. ApoE-/- mice were treated with warfarin at a dose that increased the prothrombin time (PT) more than 10-fold (250-375 microg/kg body weight/day) for 12 weeks from the age of 12 weeks onwards. The extent and composition of the vascular lipid lesions that developed were assessed using oil red O to measure neutral lipid in the vessel wall and quantitative immunofluoresence to measure fibrin(ogen) levels as well as macrophage and smooth muscle cell numbers. Mice treated with warfarin developed lesions both in the aortic sinus and the descending aorta to the same degree as mice receiving no treatment (28,351+/-350 microm2/mouse treated with war...Continue Reading

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Citations

May 17, 2005·Methods : a Companion to Methods in Enzymology·Alan Daugherty, Debra L Rateri
Jan 1, 2003·Methods : a Companion to Methods in Enzymology·Ruth Ashery-Padan
Apr 7, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Rajashree RanaAthan Kuliopulos
Dec 31, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·Rachel E TilleyNigel Mackman
Sep 27, 2003·Arteriosclerosis, Thrombosis, and Vascular Biology·Esther LutgensMat J A P Daemen
Nov 6, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·David J GraingerElaine McKilligin

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