Effects Of Aspirin/Clopidogrel On Endothelial Progenitor Cell Functions In A Rat Model Of Myocardial Infarction

Background and objective:Endothelial progenitor cells(EPCs)impairment has been shown to correlate with the progression of cardiovascular diseases including myocardial infarction(MI),suggesting pharmacological approaches against MI-initiated EPC damage is a potential therapeutic strategy.Although clinical evidence indicated antiplatelet-based therapy with aspirin and clopidogrel plays a crucial role in ischemic cardiovascular diseases,the effects on regulating EPCs and underlying mechanism still remain unclear.Here we treated a rat model of myocardial infarction with aspirin,clopidogrel,or combination of these two agents to explore their potential role in rescuing EPCs during MI and relevant mechanism involved.Method and results:Male Sprague-Dawley(SD)rats were subjected to myocadial infarction model(MI)and then treated with Aspirin(MI+AS),Clopidogrel(MI+CLO)or combination of the two drugs(MI+AS+CLO).Peripheral blood and bone marrow were collected at the indicated endpoints for EPCs study(1 week or 2 weeks post therapy).Flow cytometry anaylsis revealed a significant reduction of circulating EPCs in peripheral blood after myocardial infarction.Aspirin and Clopidogrel administration for 1 week attenuated the MI-initiated EPCs decrease in circulation as well as the combined treatment.Moreover,EPCs functional impairment happened in MI rat which were confirmed by in vitro test of the impaired migratory capacity,tube formation and adhesion.Aspirin and Clopidogrel protected BM-EPCs against myocardial ischemia-induced functional damage.Dual-drugs therapy also significantly improved tube formation and cell adhesion of BM-EPCs from myocardial infarcted rats except for cellular migration.The protective effects of Aspirin and Clopidogrel were also indicated by suppressing angiogenesis inhibitory factor thrombospondin-1(TPS-1)secretion and improving VEGF expression in BM-EPCs from MI rats.However,no significant change of VEGF expression was observed in dual-drug therapy group.Conclusion:Our study identified the protective effects of a Aspirin and Clopidogrel on myocardic ischemia-impaired EPCs,which promoted EPCs population in peripheral circulation and attenuated functional impairments of BM-EPCs in rats after myocardial ischemia.The benifical contribution of Aspirin and Clopidogrel might be related to compromised TSP-1 secretion and increased VEGF in EPCs from bone marrow.