Increased adhesion and aggregation of platelets lacking cyclic guanosine 3',5'-monophosphate kinase I

• Published in: The Journal of experimental medicine Vol. 189; no. 8; pp. 1255 - 1264
• Main Authors: Massberg, S, Sausbier, M, Klatt, P, Bauer, M, Pfeifer, A, Siess, W, Fässler, R, Ruth, P, Krombach, F, Hofmann, F
• Format: Journal Article
• Language: English
• Published: United States The Rockefeller University Press 19-04-1999
• Subjects: Animals; Blood Platelets - drug effects; Blood Platelets - enzymology; Cell Adhesion - drug effects; Cell Adhesion - genetics; Cell Adhesion Molecules - metabolism; Cell Size - genetics; Cyclic GMP - pharmacology; Cyclic GMP-Dependent Protein Kinases - deficiency; Cyclic GMP-Dependent Protein Kinases - genetics; Endothelium, Vascular - enzymology; In Vitro Techniques; Ischemia - physiopathology; Mice; Mice, Knockout; Microcirculation - physiopathology; Microfilament Proteins; Nitric Oxide - pharmacology; Phosphoproteins - metabolism; Phosphorylation; Platelet Aggregation - drug effects; Platelet Aggregation - genetics; Platelet Aggregation Inhibitors - pharmacology; Serotonin - metabolism
• ISSN: 0022-1007; 1540-9538
• DOI: 10.1084/jem.189.8.1255

Atherosclerotic vascular lesions are considered to be a major cause of ischemic diseases, including myocardial infarction and stroke. Platelet adhesion and aggregation during ischemia-reperfusion are thought to be the initial steps leading to remodeling and reocclusion 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'-monophosphate kinase I (cGKI). To test the intravascular significance of the NO/cGKI signaling pathway in vivo, we have studied platelet-endothelial cell and platelet-platelet interactions during ischemia/reperfusion using cGKI-deficient (cGKI-/-) mice. Platelet cGKI but not endothelial or smooth muscle cGKI is essential to prevent intravascular adhesion and aggregation of platelets after ischemia. The defect in platelet cGKI is not compensated by the cAMP/cAMP kinase pathway supporting the essential role of cGKI in prevention of ischemia-induced platelet adhesion and aggregation.