Abstract 1007: Platelet Glycoprotein VI (GPVI) Deletion Reduces Myocardial Infarction in Mice
Fibrillar collagen, exposed by damage of vascular endothelium, is the most thrombogenic component of the subendothelium, which, in addition to supporting platelet adhesion, is also a potent platelet activator. Platelet glycoprotein VI (GPVI) plays a major role in collagen-induced platelet activation, leading to thrombus formation. Inhibition of GPVI function may be a novel anti-platelet therapy with minimal bleeding risk. Recent evidence in FcRγ-chain-knockout (KO) mice, which also lack GPVI, shows attenuated myocardial infarction after ischemia and reperfusion. Unlike GPVI, which is exclusively expressed in platelets and megakaryocytes, FcRγ-chain also exists in white blood cells and immune cells. Thus, it is unclear whether GPVI deletion is cardioprotective. In this study, we compared myocardial infarction in GPVI-KO and age-matched wild-type (WT) mice. In parallel FcRγ-chain-KO mice were compared with age-matched WT mice. A major branch of left coronary artery was ligated for 30 min followed by reperfusion for 24 hrs. Myocardial infarction was measured by tetrozolium staining. Hemodynamics were not statistically different among the groups. Risk zone sizes were also similar between WT and GPVI-KO mice (0.020 ± 0.004 cm3 and 0.022 ± 0.005 cm3, respectively) (Mean ± SD). However, percentage infarction of the risk zone was significantly smaller in GPVI-KO mice (averaged 22 ± 8 % vs. 45 ± 18 % in WT). Comparable protection was observed in FcRγ-chain-KO mice (12 ± 6 % vs. 46 ± 13 % in WT). Significant exposure of vascular collagen in the ischemia/reperfusion region of myocardium was revealed by FITC-labeled recombinant GPVI protein, injected prior to ischemia, indicating endothelium injury. Furthermore, there was significantly less expression of P-selectin, a marker of activated platelets, in the myocardium from GPVI-KO and FcRγ-KO mice when compared with WT mice. It is concluded that deletion of GPVI reduces myocardial infarction induced by ischemia and reperfusion, likely due to the attenuation of the platelet-collagen interaction. With its known anti-thrombotic effect and minimal risk of bleeding in animals, anti-GPVI therapy may offer a promising novel treatment for cardiovascular diseases.