Abstract:

Abstract:Objective
To investigate the effect of simvastatin on replicative senescence of endothelial progenitor cells (EPCs) and to clarify the anti-senescence mechanism of simvastatin.Methods The second generation of EPCs were used as normal control group,and the eighth generation cells were divided into high dose simvastatin group,low dose simvastatin group,and replicative senescence group.The cell cycle and apoptosis,the expression of Bcl-2 protein were detected by flow  cytometry  after the next 7 d culturing.Results The early  and late apoptotic rates of the EPCs in normal control group were lower than those in the other three groups (P<0.05 or P<0.01);there was no statistical difference in the early apoptotic rates between high dose simvastatin group,low dose simvastatin group and replicative senescence(P>0.05).The differences of late apoptotic rate between replicative senescence group,high dose simvastatin group and low dose simvastatin group were statistically significant (P<0.05 or P<0.01).The percentages of EPCs in high dose simvastatin group,low dose simvastatin group and replicative senescence group were increased in the G0/G1 phase,but were  decreased in the phases of S and G2/M compared with  normal control group (P<0.01),but there was no difference between simvastatin groups and replicative senescence group(P>0.05).Compared with normal control group,the mean fluorescence intensities and the positive expression rates of Bcl-2 protein in high dose simvastatin group,low dose simvastatin group and replicative senescence group were significantly decreased(P<0.01);and the differences between high dose simvastatin group and replicative senescence group were also statistically significant(P<0.05 or P<0.01);the positive expression rate of Bcl-2 protein in low dose simvastatin group was higher than that in replicative senescence group (P<0. 01),but the difference of the mean fluorescence intensity between two groups had no statistical significance（P>0.05).Conclusion Simvastatin can reduce the replicative senescence of EPCs,and the mechanism may be related to decreasing the expression of Bcl-2 protein.
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Key words: endothelial progenitor cells, simvastatin, replicative senescence, apoptosis, Bcl-2