Increased Adhesion and Aggregation of Platelets Lacking Cyclic Guanosine 3',5'-Monophosphate Kinase I

doi:10.1084/jem.189.8.1255

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J. Exp. Med., Volume 189, Number 8, April 19, 1999 1255-1264

Increased Adhesion and Aggregation of Platelets Lacking Cyclic Guanosine 3',5'-Monophosphate Kinase I

By Steffen Massberg,^* Matthias Sausbier, Peter Klatt, Markus Bauer,^§ Alexander Pfeifer, Wolfgang Siess,^§ Reinhard Fässler, Peter Ruth, Fritz Krombach,^* and Franz Hofmann

From the ^* Institut für Chirurgische Forschung der Ludwig-Maximilians-Universität München, 81377 München, Germany; the Institut für Pharmakologie und Toxikologie der Technische Universität München, 80802 München, Germany; the ^§ Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, Klinikum Innenstadt, Universität München, 80336 München, Germany; and the Department of Experimental Pathology, Lund University, 221 85 Lund, Sweden

Atherosclerotic vascular lesions are considered to be a major cause of ischemic diseases, including myocardial infarctionand stroke. Platelet adhesion and aggregation during ischemia-reperfusionare thought to be the initial steps leading to remodeling andreocclusion of the postischemic vasculature. Nitric oxide (NO)inhibits platelet aggregation and smooth muscle proliferation.A major downstream target of NO is cyclic guanosine 3',5'-monophosphatekinase I (cGKI). To test the intravascular significance of theNO/cGKI signaling pathway in vivo, we have studied platelet-endothelialcell and platelet-platelet interactions during ischemia/reperfusionusing cGKI-deficient (cGKI^/) mice. Platelet cGKI but not endothelial or smooth muscle cGKIis essential to prevent intravascular adhesion and aggregationof platelets after ischemia. The defect in platelet cGKI is notcompensated by the cAMP/cAMP kinase pathway supporting the essentialrole of cGKI in prevention of ischemia-induced platelet adhesionandaggregation.

Key words: fluorescence microscopy; endothelial cell; microcirculation; nitric oxide; cyclic guanosine 3',5'-monophosphate-dependent protein kinase

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