Effects Of Simvastatin On Endothelial Progenitor Cell Proliferation, Migration, Apoptosis And Adhesion Affect

Objective: To investigate in vitro whether simvastatins of different concentrations have influences on the functions of endothelial progenitor cells (EPCs).Methods: Total mononuclear cells (MNCs) were isolated from human peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7 days cultured, attached cells were isolated and were assessed with a laser scanning confocal microscope, EPCs were characterized as cells double positive for DiLDL-uptake and lectin binding. EPCs were treated with simvastatins of different concentrations (0.0001,0.001,0.01,0.1,1.0μM),or LY294002(PI3K inhibitor)+ simvastatins(0.01μM) for 24h. The influences of Simvastatins on EPCs' proliferation, migration , apoptosis were assayed with MTT assay, modified Boyden chamber assay and FACS assay, respectively. EPCs adhesion assay was performed by replating those on fibronectin-coated dishes, and then the adherent cells were counted.Results: Simvastatins strikingly improved the ability in proliferating, migrating, anti-apoptosis and adhering of EPCs isolated from human peripheral blood (p<0.05). Simvastatins at 0.01μM concentration reached the maximum effect on EPCs. While the concentration of simvastatins was further increased more than 0.01μM, the above improvement effects showed a tendency to decline, but the effects at 0.1μM concentration were still greater than those in control group. And the influence of Simvastatins on these functions of EPCs could be abolished by LY294002(PI3K inhibitor).Conclusion: The present study established that Simvastatins could improve EPCs' proliferation, migration , anti-apoptosis and adhesion and the mechanism maybe involves the PI3K/AKt pathway.