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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Thrombomodulin is required for the antithrombotic activity of thrombin mutant W215A/E217A in a mouse model of arterial thrombosis

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Author(s):
Vicente, Cristina P. [1] ; Weiler, Hartmut [2] ; Di Cera, Enrico [3] ; Tollefsen, Douglas M. [4]
Total Authors: 4
Affiliation:
[1] Univ Estadual Campinas, UNICAMP, Inst Biol, Dept Anat Cellular Biol Physiol & Biophys, Sao Paulo - Brazil
[2] Blood Ctr Wisconsin, Milwaukee, WI - USA
[3] St Louis Univ, Dept Biochem, St Louis, MO 63103 - USA
[4] Washington Univ, Sch Med, Div Hematol, St Louis, MO 63110 - USA
Total Affiliations: 4
Document type: Journal article
Source: THROMBOSIS RESEARCH; v. 130, n. 4, p. 646-648, OCT 2012.
Web of Science Citations: 3
Abstract

Introduction: 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. Materials and methods: To assess the role of thrombomodulin, we administered WE thrombin to thrombomodulin-deficient (TMPro/Pro) mice and measured the time to occlusive thrombus formation in the carotid artery after photochemical injury of the endothelium. Results and conclusions: Doses of WE thrombin >= 10 mu g/kg prolonged the thrombosis time of wild-type mice (> 1.6-fold), while doses >= 100 mu g/kg only slightly prolonged the thrombosis time of TMPro/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. (c) 2011 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 10/11474-5 - Influence of glycosaminoglycans in inflammation and cellular therapy using endothelial progenitor cells after arterial injury in mice
Grantee:Cristina Pontes Vicente
Support Opportunities: Regular Research Grants