Effects of Rosiglitazone on the Proliferation of Vascular Smooth Muscle Cell Induced by High Glucose

Aim To investigate the effects of the sensitizer rosiglitazone on the proliferation of vascular smooth muscle cell (VSMC) induced by high glucose administration. Methods VSMCs were isolated from rat thoracic aortas and cultured in 10% fetal bovine serum (FBS). VSMC proliferation was evaluated by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and cell counting. The cell cycle was examined by flow cytometry. The protein expressions of proliferating cell nuclear antigen (PCNA) and matrix metalloproteinases-2 (MMP-2) were evaluated by Western blotting. MMP-2 mRNA expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and gelatinolytic activity was determined by zymography. Results Promoted VSMC proliferation significantly increased the number of VSMCs in the S phase, the expressions of PCNA and MMP-2, and MMP-2 activity, as well as decreased the proportion of VSMCs in the G(0)/G(1) phase. Rosiglitazone at a concentration of 10 mu mol/L markedly inhibited glucose-induced VSMC proliferation (1.869 +/- 0.22 vs 0.820 +/- 0.15, P < 0.01). Concomitantly, rosiglitazone inhibited PCNA expression (0.96 +/- 0.07 vs 0.75 +/- 0.06, P < 0.05) and cell cycle progression from G(0)/G(1) to S phase (the proportion of VSMCs in the G(0)/G(1) and S phase were 69.6 +/- 3.96% vs 84.3 +/- 1.73% and 25.2 +/- 1.73% vs 10.1 +/- 1.42% (P < 0.01), respectively). Furthermore, rosiglitazone significantly decreased MMP-2 mRNA expression (0.98 +/- 0.08 vs 0.71 +/- 0.05, P < 0.05), protein expression (0.80 +/- 0.04 vs 0.64 +/- 0.03, P < 0.05) and MMP-2 activity (320 +/- 25% vs 248 +/- 21%, P < 0.05). Conclusion Rosiglitazone significantly inhibited VSMC proliferation, at least in part by inhibiting high glucose-induced G(1)-> S phase transition, PCNA expression and MMP-2 synthesis.