Different effects of simvustatin on proliferation of rat smooth muscle progenitor cells versus endothelial progenitor cells / 中华老年医学杂志

ABSTRACT

Objective To investigate the different influences of simvastatin on proliferation of rat smooth muscle progenitor cells(SPCs) versus endothelial progenitor cells (EPCs) and identify the compounds that differentially inhibit SPCs and EPCs proliferation for clinical usefulness. Methods Total mononuclear cells (MNCs) were isolated from bone marrow of rats by Fieoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. SPCs outgrew from the culture of MNCs in the presence of platelet-derived growth factor-BB and basic fibroblast growth factor, whereas EPCs were obtained in the presence of vascular endothelial growth factor. SPCs were identified as adherent cells positive for α-smooth muscle actin (α-SMA) by indirect immunofluoreseent staining. EPCs were characterized as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining. SPCs and EPCs were stimulated by simvastatin (0.01～10.00 μmol/L) or vehicle control for the respective time points (6 h, 12 h, 24 h and 48 h). SPCs and EPCs proliferation were assayed with 3H-TdR incorporation and manual counting respectively. Results Simvastatin obviously inhibited SPCs proliferation. At the concentration of 0. 01 μmol/L for 12 h,simvastatin significantly reduced the number of SPCs by (5.8±3.1)% compared with control group (P<0.05). Simvastatin significantly stimulated EPCs proliferation, which was dose- and time dependent and reached maximum at 1 μmol/L after 24 hours (2.0±0.1 fold increase, P<0.01).Conclusions Simvastatin displays different effects on SPCs (inhibited) and EPCs (promoted)proliferation. Local application of simvastatin may inhibit arterial restenosis and promote reendothelialization of injured vessels.