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Blood, 1 August 2008, Vol. 112, No. 3, pp. 603-609. Prepublished online as a Blood First Edition Paper on May 16, 2008; DOI 10.1182/blood-2008-02-142943. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-02-142943v1 112/3/603    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 Marx, I. Articles by Denis, C. V. Search for Related Content PubMed PubMed Citation Articles by Marx, I. Articles by Denis, C. V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Altered thrombus formation in von Willebrand factor–deficient mice expressing von Willebrand factor variants with defective binding to collagen or GPIIbIIIa Isabelle Marx1,2, Olivier D. Christophe1, Peter J. Lenting3, Alain Rupin2, Marie-Odile Vallez2, Tony J. Verbeuren2, and Cécile V. Denis1 1 Inserm U770 and Universite Paris-Sud, Le Kremlin-Bicêtre, France; 2 Division of Angiology, Servier Research Institute, Suresnes, France; and 3 Laboratory for Thrombosis and Haemostasis, Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands The role of von Willebrand factor (VWF) in thrombosis involves its binding to a number of ligands. To investigate the relative importance of these particular interactions in the thrombosis process, we have introduced mutations into murine VWF (mVWF) cDNA inhibiting VWF binding to glycoprotein (Gp) Ib, GPIIbIIIa, or to fibrillar collagen. These VWF mutants were expressed in VWF-deficient mice (VWF–/–) by using an hydrodynamic injection approach, and the mice were studied in the ferric chloride–induced injury model. Expression of the collagen and the GPIIbIIIa VWF-binding mutants in VWF–/– mice resulted in delayed thrombus growth and significantly increased vessel occlusion times compared with mice expressing wild-type (WT) mVWF (30 ± 3 minutes and 38 ± 4 minutes for the collagen and GPIIbIIIa mutants, respectively, vs 19 ± 3 minutes for WT mVWF). Interestingly, these mutants were able to correct bleeding time as efficiently as WT mVWF. In contrast, VWF–/– mice expressing the GPIb binding mutant failed to restore thrombus formation and were bleeding for as long as they were observed, confirming the critical importance of the VWF-GPIb interaction. Our observations suggest that targeting the VWF-collagen or VWF-GPIIbIIIa interactions could be an interesting alternative for new antithrombotic strategies. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Momi, E. Falcinelli, S. Giannini, L. Ruggeri, L. Cecchetti, T. Corazzi, C. Libert, and P. Gresele Loss of matrix metalloproteinase 2 in platelets reduces arterial thrombosis in vivo J. Exp. Med., October 26, 2009; 206(11): 2365 - 2379. [Abstract] [Full Text] [PDF] A. F. Riddell, K. Gomez, C. M. Millar, G. Mellars, S. Gill, S. A. Brown, M. Sutherland, M. A. Laffan, and T. A. J. McKinnon Characterization of W1745C and S1783A: 2 novel mutations causing defective collagen binding in the A3 domain of von Willebrand factor Blood, October 15, 2009; 114(16): 3489 - 3496. [Abstract] [Full Text] [PDF] S. F. De Meyer, H. Deckmyn, and K. Vanhoorelbeke von Willebrand factor to the rescue Blood, May 21, 2009; 113(21): 5049 - 5057. [Abstract] [Full Text] [PDF]

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