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Blood, 1 January 2004, Vol. 103, No. 1, pp. 136-142.
Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2002-11-3417.
 Previous Article | Table of Contents | Next Article 
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)–deficient mice
Steffen Massberg,
Sabine Grüner,
Ildiko Konrad,
Maisa I. Garcia Arguinzonis,
Martin Eigenthaler,
Kathrin Hemler,
Julia Kersting,
Christian Schulz,
Iris Müller,
Felicitas Besta,
Bernhard Nieswandt,
Ulrich Heinzmann,
Ulrich Walter, and
Meinrad Gawaz
From the Deutsches Herzzentrum und 1 Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany; GSF (Gesellschaft für Strahlenforschung) National Research Center for Environment and Health, Institute of Pathology, Neuherberg, Germany; Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Germany; and Institut für Klinische Biochemie und Pathobiochemie, Universität Würzburg, Germany.
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 cyclic adenosine monophosphate (cAMP)– and cyclic guanosine monophosphate (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 physiologic conditions, platelet adhesion to endothelial cells was significantly enhanced in VASP null mutants when compared with wild-type mice (P < .05). Platelet recruitment in VASP null mice involved P-selectin and the fibrinogen receptor glycoprotein IIb-IIIa (GPIIb-IIIa). Under pathophysiologic 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 < .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 physiologic and pathophysiologic conditions.
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