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Title: Synergistic effect of thrombin on collagen-induced platelet procoagulant activity is mediated through protease-activated receptor-1
Authors: Keuren, Jeffrey F W ×
Wielders, Simone J H
Ulrichts, Hans
Hackeng, Tilman
Heemskerk, Johan W M
Deckmyn, Hans
Bevers, Edouard M
Lindhout, Theo #
Issue Date: Jul-2005
Publisher: Lippincott williams & wilkins
Series Title: Arteriosclerosis, Thrombosis and Vascular Biology vol:25 issue:7 pages:1499-1505
Abstract: OBJECTIVE: In the blood coagulation process, the rate of thrombin formation is critically dependent on phosphatidylserine (PtdSer) at the surface of activated platelets. Thrombin synergistically enhances the collagen-induced platelet procoagulant response. The objective of this study is to elucidate the mechanism of this synergistic action with a focus on the intracellular Ca2+ concentration ([Ca2+]i) and the various platelet receptors for thrombin. METHODS AND RESULTS: We demonstrate that procoagulant activity is related to a sustained increased [Ca2+]i, which in turn depends on extracellular Ca2+ influx. Increased PtdSer exposure coincides with increased [Ca2+]i and was observed in a subpopulation (approximately 14%) of the platelets after stimulation with thrombin plus collagen. 2D2-Fab fragments against the thrombin binding site on GPIbalpha made clear that this receptor did not signal for platelet procoagulant activity. Inhibition of protease-activated receptor 1 (PAR-1) and PAR-4 by selective intracellular inhibitors and selective desensitization of these receptors revealed that PAR-1, but not PAR-4, activation is a prerequisite for both sustained elevations in [Ca2+]i and procoagulant activity induced by collagen plus thrombin. CONCLUSIONS: The interaction of thrombin with PAR-1 mediates a synergistic effect on collagen-induced procoagulant activity by inducing a sustained elevation in [Ca2+]i in a subpopulation of platelets.
ISSN: 1079-5642
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Chemistry, Campus Kulak Kortrijk
× corresponding author
# (joint) last author

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