Antiangiogenic Effect of Platelet P2Y(12) Inhibitor in Ischemia-Induced Angiogenesis in Mice Hindlimb

PURPOSE: Postischemic inflammation induces angiogenesis, while platelet P2Y(12) inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y(12) inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia. METHODS: Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production. RESULTS: Ischemic hindlimb angiogenesis was sharply decreased in IL-10(+/+) mice than IL-10(−/−) mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10(+/+) mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10(–/–)) C57BL/6J mice. CONCLUSION: The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.