To investigate the effects of simvastatin on differentiation and proliferation of rat smooth muscle progenitor cells (SPCs) and identification of compounds that inhibit SPCs differentiation and proliferation for substantial clinical usefulness.Methods
Total mononuclear cells (MNCs) were isolated from marrow of rats by Ficoll density gradient centrifugation method, and then plated on fibronectin-coated culture dishes. Fresh isolated MNCs were treated with simvastatin (0.01∼10 μmol/l) or vehicle control for 8 d. SPCs were characterised as adherent cells positive for α-SMA by indirect immunofluorescent staining. After 8 days cultured, attached cells were treated with simvastatin (0.01∼10 μmol/l) or vehicle control for 24 h. The proliferation and migration of SPCs were assayed with 3H-TdR incorporation and modified Boyden chamber assay respectively. SPCs adhesion assay was performed by replating those on fibronectin-coated dishes and counting the adherent cells.Results
Simvastatin potently inhibited SPCs outgrowth. The number of SPCs at 8 days was dramatically decreased by simvatatin. At a concentration as low as 0.01 μmol/l, simvastatin significantly reduced 7.5 ± 5.4% of SPCs (0.01 μmol/l simvastatin vs control: 79 ± 5 vs 85 ± 4, n = 5, p < 0.05). Simvastatin also inhibited SPCs proliferation in a dose-dependent manner, simvastatin significantly reduced 5.8 ± 3.1% of SPCs at a concentration as low as 0.01 μmol/l for 24 h (0.01 μmol/l simvastatin vs control: 3833 ± 126 vs 4070 ± 184, n = 5, p < 0.05). In addition, sirolims also inhibited SPCs migratory and adhesive capacity in a concentration-dependent manner.Conclusion
Simvastatin could inhibit the differentiation, proliferation and migration of rat smooth muscle progenitor cells.