Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice.

Massberg, S; Grüner, S; Konrad, I; Garcia Arguinzonis, MI; Eigenthaler, M; Hemler, K; Kersting, J; Schulz, C; Muller, I; Besta, F; Nieswandt, B; Heinzmann, U; Walter, U; Gawaz, M

doi:10.1182/blood-2002-11-3417

2004

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Title:: Enhanced in vivo platelet adhesion in vasodilator-stimulated phosphoprotein (VASP)-deficient mice.
Document type:: Journal Article
Author(s):: Massberg, S; Grüner, S; Konrad, I; Garcia Arguinzonis, MI; Eigenthaler, M; Hemler, K; Kersting, J; Schulz, C; Muller, I; Besta, F; Nieswandt, B; Heinzmann, U; Walter, U; Gawaz, M
Abstract:: 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.
Journal title abbreviation:: Blood
Year:: 2004
Journal volume:: 103
Journal issue:: 1
Pages contribution:: 136-42
Language:: eng
Fulltext / DOI:: doi:10.1182/blood-2002-11-3417
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/12933589
Print-ISSN:: 0006-4971
TUM Institution:: I. Medizinische Klinik und Poliklinik (Kardiologie)
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Innere Medizin I, Kardiologie (Prof. Laugwitz)2004