Effects of simvastatin on nicotine-induced t-PA and PAI-1 expression in human umbilical vein endothelial cells

AIM: To investigate the effects of simvastatin on nicotine-induced expression of tissue plasminogen activator(t-PA) and plasminogen activator inhibitor-1(PAI-1) at mRNA and protein levels in human umbilical vein endothelial cells(HUVECs).METHODS: Cultured HUVECs at passage 3 to 6 were randomly divided into control group,nicotine group and simvastatin groups.The cells in simvastatin groups were treated with simvastatin at the concentrations of 1,10 and 100 μmol/L for 2 h,and then exposed to nicotine at the concentration of 100 μmol/L for 24 h.The production of t-PA and PAI-1 in the cultured medium was measured by enzyme-linked immunosorbent assay(ELISA).The mRNA expression of t-PA and PAI-1 was determined by reverse transcript-polymerase chain reaction(RT-PCR).RESULTS: Compared with the control cells,the secretion and mRNA expression of PAI-1 in the cells treated with nicotine were significantly increased(P0.05).Simvastatin decreased the secretion and mRNA expression of PAI-1 in HUVECs stimulated by nicotine in a dose-dependent manner,and the most notable inhibitory effect was observed in 100μmol/L simvastatin group,in which the level of PAI-1 was almost the same as that in the control cells(P0.05).Compared with the control cells,nicotine inhibited the mRNA expression of t-PA in HUVECs(P0.05),and simvastatin at the concentrations of 10 and 100 μmol/L markedly increased the mRNA expression of t-PA in HUVECs treated with nicotine.However,the production of t-PA remained no significantly different among groups(P0.05).CONCLUSION: Simvastatin obviously decreases the expression of PAI-1 at mRNA and protein levels,increases the mRNA expression of t-PA,and improves the fibrinolytic function of HUVECs exposed to nicotine in vitro.