Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 39, Issue 6, Pages 856-864Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2005.07.006
Keywords
reperfusion; Fc receptor gamma-chain; platelet; glycoprotein; von Willebrand factor
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Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor gamma-chain (FcR gamma) is coexpressed with glycoprotein (GP) VI, forming a platelet collagen receptor, and the activation of platelets by collagen is closely coupled with tyrosine phosphorylation of the FcR gamma. To examine the functional significance of platelet FcR gamma/GPVI complex in the early phase of myocardial ischemia and reperfusion injury in mice, we performed coronary occlusion and reperfusion experiments using wild type mice and FcR gamma-deficient (FcR gamma(-/-)) mice that lack GPVI. The infarct size was significantly smaller in FcR gamma(-/-) mice subjected to occlusion and reperfusion of the coronary artery than in control FcR gamma(+/+) mice. Twenty-four hours after the reperfusion, electron microscopy of the injured tissue showed substantially more platelet aggregation and occlusive platelet microthrombi in the capillaries of the damaged areas of the wild type mice than in those of the FcR gamma(-/-) mice. Platelet Syk was scarcely activated in the FcR gamma(-/-) mice after myocardial ischemia and reperfusion, but significantly activated in the FcR gamma(+/+) mice. CD11b expression on neutrophils was elevated after myocardial ischemia and reperfusion in both mouse groups, whereas myeloperoxidase activity in the injured areas was significantly lower in the FcR gamma(-/-) mice than in the FcR gamma(+/+) mice. These results suggest that the collagen-induced activation of platelets through the FcR gamma plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcR gamma and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury. (c) 2005 Elsevier Ltd. All rights reserved.
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