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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-05-1470. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-05-1470v1 100/9/3240    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Weiss, E. J. Articles by Coughlin, S. R. Search for Related Content PubMed PubMed Citation Articles by Weiss, E. J. Articles by Coughlin, S. R. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2002, Vol. 100, No. 9, pp. 3240-3244 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Protection against thrombosis in mice lacking PAR3 Ethan J. Weiss, Justin R. Hamilton, Katy E. Lease, and Shaun R. Coughlin From the Cardiovascular Research Institute, Department of Medicine, and Department of Cellular and Molecular Pharmacology, University of California, San Francisco. The recent observation that knock-out of protease-activated receptor-4 (PAR4) ablates thrombin signaling in mouse platelets and protects against ferric chloride-induced thrombosis of mouse mesenteric arterioles suggests that thrombin's actions on platelets can play an important role in thrombosis. Complete ablation of thrombin signaling would be difficult to achieve in human beings because human platelets have 2 thrombin receptors that are each capable of mediating transmembrane signaling. However, it is possible that complete ablation of thrombin signaling in platelets is not necessary for an antithrombotic effect. In mouse platelets, PAR3 functions as a cofactor that binds thrombin and promotes productive cleavage of PAR4, and thrombin responses are decreased but not absent in Par3/ platelets. We now report that Par3/ mice were protected against ferric chloride-induced thrombosis of mesenteric arterioles and against thromboplastin-induced pulmonary embolism. Surprisingly, Par3/ and Par4/ mice showed similar degrees of protection in these models and similar prolongation of tail bleeding times. Thus, even a partial decrease in mouse platelet responsiveness to thrombin protected against thrombosis and impaired hemostasis in some settings. These results demonstrate the importance of PAR3's unusual cofactor function and underscore the relative importance of thrombin's actions on platelets in vivo. They also suggest that PAR inhibition might be explored for the prevention or treatment of thrombosis in human beings. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M.-C. Cathcart, R. Tamosiuniene, G. Chen, T. G. Neilan, A. Bradford, K. J. O'Byrne, D. J. Fitzgerald, and G. P. Pidgeon Cyclooxygenase-2-Linked Attenuation of Hypoxia-Induced Pulmonary Hypertension and Intravascular Thrombosis J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 51 - 58. [Abstract] [Full Text] [PDF] R. A. Schuepbach, C. Feistritzer, L. F. Brass, and M. 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