Inhibition Of Leptin-induced Endothelin-1 Expression By Atorvastatin Through Extracellular Signal-regulated Kinase Signaling Pathway In Vascular Smooth Muscle Cells

OBJECTIVE:To investigate the effects of atorvastatin on leptin induced endothelin-1 expression in Vascular Smooth Muscle Cells and reveal the signal pathway.METHORDS:Vascular smooth muscle cells (VSMCs) were isolated and cultured from the aortas of 8-10-week-old male mice. The protein and mRNA levels of endothelin-1 expression were detected by enzyme linked immunosorbent assay and reverse transcription polymerase chain reaction (RT-PCR) respectively. The extracellular signal regulated kinase (ERK) 1/2 activation was analyzed by Western blotting.RESULTS:Leptin treatment caused a time-dependent increase in endothelin-1 expression. The protein of endothelin-1 treated by atorvastatin was lower than that of the leptin stimulation group at dose-dependent. The phosphorylation level of ERK 1/2 was enhanced by leptin stimulation and the leptin induced phosphorylation of ERK1/2 decreased after 10 micromol/L atorvastatin stimulation. CONCLUSION:Atorvastatin decreases the leptin induced endothelin-1 expression in VSMCs while atorvastatin at 1-10 micromol/L concentration-dependently through inhibiting the activation of ERK1/2.