Abstract: ABSTRACT:Objective To examine the mechanisms by which the peroxisome proliferator-activated receptors (PPARs )-mediated pathways contribute to the antiplatelet activity of simvastatin.Methods Blood samples were donated from healthy volunteers in order to prepare human platelet suspensions.The effects of simvastatin on collagen-induced platelet activation and the activity of PPARs were measured by impedance aggregometry,flow cytometric analysis, enzyme-linked immunosorbent assay,and spectrofluorimetry.Results Simvastatin induced PPARα and PPARγ activation in a dose-dependent manner in platelet suspensions (P < 0.05). Additionally,simvastatin inhibited collagen-induced platelet aggregation,expression of CD62 and PAC-1,and Ca2+ mobilization.These effects of simvastatin on platelet responses were strongly reduced by adding selective PPARγ antagonist (P <0.05),but not PPARα antagonist.Conclusion Simvastin inhibition of platelet activation induced by collagen is mediated by PPARγ-dependent processes.

Key words: platelet activation, peroxisome proliferator-activated receptors, simvastin