Effect of endothelin-1 stimulation on peroxisome proliferator-activated receptor-gamma expression in vascular smooth muscle cells

OBJECTIVE: To investigate the effect of endothelin-1 (ET-1) on the expression of peroxisome proliferators-activated receptor-gamma in vascular smooth muscle cells. METHODS: The first to the third passages of aortic vascular smooth muscle cells (VSMCs) isolated from 16-week-old Wistar rats were cultured in vitro and stimulated by ET-1 for 12, 24, 48, and 72 h, respectively, and at different concentrations of ET-1 for 48 h. PPAR-gamma mRNA expression of the cells was detected by reverse transcription (RT)-PCR and PPAR-gamma protein by Western blotting after the stimulations, and the proliferation of VSMCs was evaluated by MTT assay. RESULTS: No changes in PPAR-gamma mRNA and protein expressions were observed in the VSMCs after ET-1 stimulation for 12 h (P>0.05), and when the stimulation was prolonged to 24 h, slight decrease in the expressions occurred but the difference was not statistically significant in comparison with the control group (P<0.05). After 48 to 72 hour's ET-1 stimulation, the expressions of both PPAR-gamma mRNA and protein were markedly decreased as compares with the control group (P<0.01). The expressions of PPAR-gamma in mRNA and protein were both decreased with the increase of ET-1 concentration after stimulation for 48 h. VSMC proliferation occurred at 12 h during ET-1 stimulation and increased with time and ET-1 concentration. CONCLUSION: ET-1 stimulation can induce VSMC proliferation and decrease the expressions of both PPAR-gamma mRNA and protein.