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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2002-11-3417. This Article Full Text (PDF) All Versions of this Article: 2002-11-3417v1 103/1/136    most recent Alert me when this article is cited Alert me if a correction is posted 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 Massberg, S. Articles by Gawaz, M. Search for Related Content PubMed PubMed Citation Articles by Massberg, S. Articles by Gawaz, M. Social Bookmarking                   What's this? Submitted November 15, 2002 Accepted July 28, 2003 Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice Steffen Massberg*, Sabine Gruener, Ildiko Konrad, Maisa I Garcia Arguinzonis, Martin Eigenthaler, Kathrin Hemler, Julia Kersting, Christian Schulz, Iris Mueller, Felicitas Besta, Bernhard Nieswandt, Ulrich Heinzmann, Ulrich Walter, and Meinrad Gawaz Deutsches Herzzentrum und 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universitaet Muenchen, Munich, Germany Institut fur Klinische Biochemie und Pathobiochemie, Universitaet Wuerzburg, Wuerzburg, Germany Rudolf Virchow Center for Experimental Biomedicine, Universitaet Wuerzburg, Wuerzburg, Germany Institute of Pathology, GSF National Research Center for Environment and Health, Munich, Germany * Corresponding author; email: massberg{at}dhm.mhn.de. Platelet adhesion and activation at the vascular wall are the initial steps leading to arterial thrombosis and vascular occlusion. Prostacyclin and nitric oxide inhibit platelet adhesion, acting via cAMP- and cGMP-dependent protein kinases. A major downstream target for both cAMP- and cGMP-dependent protein kinases is the vasodilator-stimulated phosphoprotein (VASP). To test the significance of VASP for the regulation of platelet adhesion in vivo, we studied platelet-vessel wall interactions using VASP-deficient (VASP -/-) mice. Under physiological conditions, platelet adhesion to endothelial cells was significantly enhanced in VASP null mutants, when compared to wild type mice (P < 0.05). Platelet recruitment in VASP null mice involved P-selectin and the fibrinogen receptor GPIIb-IIIa. Under pathophysiological conditions, the loss of VASP increased platelet adhesion to the postischemic intestinal microvasculature, to the atherosclerotic endothelium of ApoE-deficient mice, and to the subendothelial matrix following endothelial denudation (P < 0.05 vs. wild type). Importantly, platelet adhesion in VASP null mutants was unresponsive to nitric oxide. These data show for the first time in vivo that VASP is involved in down-regulation of platelet adhesion to the vascular wall under both physiological and pathophysiological conditions. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. E. Bear and F. B. Gertler Ena/VASP: towards resolving a pointed controversy at the barbed end J. Cell Sci., June 15, 2009; 122(12): 1947 - 1953. [Abstract] [Full Text] [PDF] A. Schafer, D. Fraccarollo, J. Widder, M. Eigenthaler, G. Ertl, and J. Bauersachs Inhibition of platelet activation in rats with severe congestive heart failure by a novel endothelial nitric oxide synthase transcription enhancer Eur J Heart Fail, April 1, 2009; 11(4): 336 - 341. [Abstract] [Full Text] [PDF] V. Mirakaj, D. Kohler, P. Rosenberger, R. L. Nachman, and S. Rafii Platelets and the Vascular Wall N. Engl. 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