ASSA14-03-37 Study of effects of simvastatin on proliferation, migration and adhension of rat smooth muscle progenitor cells

Abstract

<h3>Background</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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 &lt; 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 &lt; 0.05). In addition, sirolims also inhibited SPCs migratory and adhesive capacity in a concentration-dependent manner. <h3>Conclusion</h3> Simvastatin could inhibit the differentiation, proliferation and migration of rat smooth muscle progenitor cells.