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

Autor(es)

Vicente, Cristina P. ^[1] ; Weiler, Hartmut ^[2] ; Di Cera, Enrico ^[3] ; Tollefsen, Douglas M. ^[4]

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: THROMBOSIS RESEARCH; v. 130, n. 4, p. 646-648, OCT 2012.
• Citações Web of Science: 3

Resumo

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)

• Processo FAPESP: 10/11474-5 - Influência de glicosaminoglicanos na inflamação e terapia celular utilizando células progenitoras endoteliais após a lesão arterial em camundongos
• Beneficiário: Cristina Pontes Vicente
• Modalidade de apoio: Auxílio à Pesquisa - Regular