Objective To investigate whether fluvastatin and simvastatin have influences on endothelial progenitor cells (EPCs). Methods Total mononuclear cells (MNCs) were isolated from 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 stimulated with fluvastatin (to make a series of final concentrations: 0.01 μmol/L, 0.1 μmol/L, 1 μmol/L, 10 μmol/L), simvastatin (1 μmol/L) or vehicle control for the respective time points(6 h,12 h,24 h and 48 h). EPCs were characterized as
adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining. EPCs proliferation, migration were assayed with MTT assay and modified Boyden chamber assay, respectively. EPCs adhesion assay was performed by replating those on fibronectin-coated dishes, and then adherent cells were counted.
Results Incubation of isolated human MNCs with fluvastatin dose and time dependently increased the number of EPCs, maximum at 1 μmol/L, 24 hours (2.5-fold increase, P<0.05). In addition, fluvastatin also promote EPCs proliferative, migratory and adhesive capacity in a concentration-dependent manner. There was no statistical difference between the effects of fluvastatin on EPCs and those of simvastatin at the same concentration (P>0.05). Conclusion The results of the present study defined a novel mechanism of action of statin: the augmentation of EPCs with enhanced functional
activity.