Platelets activated by collagen through the immunoreceptor tyrosine-based activation motif in the Fc receptor γ-chain play a pivotal role in the development of myocardial ischemia-reperfusion injury

Platelet activation and the formation of platelet microaggregates in coronary vessels play pivotal roles in myocardial ischemia and reperfusion injury. The Fc receptor γ-chain (FcR γ) 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 FcRγ. To examine the functional significance of platelet FcR γ/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 FcRγ-deficient (FcRγ–/–) mice that lack GPVI. The infarct size was significantly smaller in FcRγ–/– mice subjected to occlusion and reperfusion of the coronary artery than in control FcR γ+/+ 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 γ–/– mice. Platelet Syk was scarcely activated in the FcR γ–/– mice after myocardial ischemia and reperfusion, but significantly activated in the FcR γ+/+ 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 FcRγ–/– mice than in the FcRγ+/+ mice. These results suggest that the collagen-induced activation of platelets through the FcR γ plays a pivotal role in the extension of myocardial ischemia-reperfusion injury. FcRγ and GPVI may be important therapeutic targets for myocardial ischemia-reperfusion injury.