Effects of atorvastatin on expression of PAPP-A induced by TNF-α and IL-1β in rat aortic endothelial cells

AIM: To investigate the effects of atorvastatin on the expression of pregnancy-associated plasma protein A(PAPP-A)induced by TNF-α and IL-1β in endothelial cells.METHODS: The rat aortic endothelial cells were isolated from thoracic aortas and cultured by the tissue explant method.The cells in passage 3-4 were used in the experiment and were randomly divided into 4 groups: blank control group: the cells were treated without any intervention;atorvastatin concentration groups: the cells were incubated with atorvastatin at the concentrations of 0.1,1 and 10 μmol/L for 24 h;atorvastatin time groups: the cells were incubated with atorvastatin at the concentration of 10 μmol/L for 6 h,12 h and 24 h;atorvastatin+inflammatory factors groups: the cells were pre-incubated with 60 μg/L TNF-α or 20 μg/L IL-1β for 1 h,then different concentrations of atorvastatin(0.1,1.0,10 μmol/L) were added for 6 h,12 h and 24 h.MTT reduction assay was used to observe the cell proliferation.The mRNA expression of PAPP-A was detected by RT-PCR.The protein level of PAPP-A in the supernatants of cultured cells was measured by ELISA.RESULTS: Compared with blank control group,no significant change of cell proliferation was observed after the intervention of atorvastatin and TNF-α/IL-1β for 3 h,6 h,12 h,24 h and 48 h,indicating that the drugs had no toxic effects on the cells.No significant difference of PAPP-A expression between atorvastatin groups and blank control groups was found.Compared with TNF-α groups and IL-1β groups,PAPP-A expressions in atorvastatin intervention groups significantly decreased.The protein level of PAPP-A was gradually decreased with the raised concentration of atorvastatin and the prolonged time in a concentration-and time-dependent manner.CONCLUSION: Atorvastatin doesn't influence the PAPP-A expression,but inhibits the expression of PAPP-A activated by inflammatory factors in a concentration-and time-dependent manner in primary cultured rat aortic endothelial cells.