Increased adhesion and aggregation of platelets lacking cyclic guanosine 3',5'-monophosphate kinase I.
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.
Massberg
S
S
Institut für Chirurgische Forschung der Ludwig-Maximilians-Universität München, 81377 München, Germany.
Sausbier
M
M
Klatt
P
P
Bauer
M
M
Pfeifer
A
A
Siess
W
W
Fässler
R
R
Ruth
P
P
Krombach
F
F
Hofmann
F
F
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000378:metabolism; D048429:Cell Size / Q000235:genetics; D006152:Cyclic GMP / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency* / Q000235:genetics; D004730:Endothelium, Vascular / Q000201:enzymology; D066298:In Vitro Techniques; D007511:Ischemia / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008833:Microcirculation / Q000503:physiopathology; D008840:Microfilament Proteins; D009569:Nitric Oxide / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects / Q000235:genetics*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010975:Platelet Aggregation Inhibitors; D000098662:Vasodilator-Stimulated Phosphoprotein; D009569:Nitric Oxide; D012701:Serotonin; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP