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Type: Artigo de periódico
Title: Thrombomodulin Is Required For The Antithrombotic Activity Of Thrombin Mutant W215a/e217a In A Mouse Model Of Arterial Thrombosis.
Author: Vicente, Cristina P
Weiler, Hartmut
Di Cera, Enrico
Tollefsen, Douglas M
Abstract: The thrombin mutant W215A/E217A (WE thrombin) has greatly reduced procoagulant activity, but it activates protein C in the presence of thrombomodulin and inhibits binding of platelet glycoprotein Ib to von Willebrand factor and collagen under flow conditions. Both thrombomodulin-dependent protein C activation and inhibition of platelet adhesion could contribute to the antithrombotic activity of WE thrombin. To assess the role of thrombomodulin, we administered WE thrombin to thrombomodulin-deficient (TM(Pro/Pro)) mice and measured the time to occlusive thrombus formation in the carotid artery after photochemical injury of the endothelium. Doses of WE thrombin ≥10μg/kg prolonged the thrombosis time of wild-type mice (>1.6-fold), while doses ≥100μg/kg only slightly prolonged the thrombosis time of TM(Pro/Pro) mice. We conclude that thrombomodulin plays a predominate role in mediating the antithrombotic effect of WE thrombin in the arterial circulation of mice after endothelial injury. Thrombomodulin-independent effects may occur only when high doses of WE thrombin are administered.
Subject: Animals
Carotid Arteries
Carotid Artery Thrombosis
Fibrinolytic Agents
Gene Deletion
Mice, Inbred C57bl
Point Mutation
Protein Engineering
Citation: Thrombosis Research. v. 130, n. 4, p. 646-8, 2012-Oct.
Rights: fechado
Identifier DOI: 10.1016/j.thromres.2011.11.026
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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