Effects Of Bezafibrate On The ENOS Expression Of Cultured Endothelial Cells Induced By Ox-LDL And The Role Of LOX-1

Objective: To observe the influence of oxidized low density lipoprotein (ox-LDL) on the eNOS and the expression of LOX-1 of cultured human umbilical vein endothelial cells(HUVECs).To investigate the influence and the mechanism of bezafibrate,which is agonist of peroxisome proliferator-activated receptorα,on the eNOS of cultured endothelial cells induced by ox-LDL.Methods: Human umbilical vein endothelial cells were isolated from freshly obtained human umbilical cord by collagenase treatment.The cells were cultured in DMEM culture medium. HUVECs from 4,5 generations are applied to experiment.Five groups were selected for the study: (1)control group: the normal cultured HUVECs; (2)ox-LDLgroup:HUVECs were coincubated with 50mg/L ox-LDL for 24h; (3) LOX-1 inhibitor group: HUVECs were pretreated with with 250μg/mL Poly(I) for 2h, then was incubated with 50 mg/L ox-LDL group; (4)middle concentration bezafibrate group: HUVECs were pretreated with middle concentration bezafibrate(100mmol/mL) for 2h,then incubated with 50 mg/L ox-LDL for 24h; (5)100 mmol/mL benzafibrate and LOX-1 inhibitor group: HUVECs were pretreated with 250μg/mL Poly(I) for 2h, then was incubated with 100 mmol/mL benzafibrate 50 mg/L for 2h,then incubated with 50 mg/L ox-LDL for 24h. LOX-1 mRNA, eNOS mRNA were detected by RT-PCR ; LOX-1,eNOS protein were detected by Wester-blot.Results: (1) Compared with the control group,ox-LDL could obviously increase LOX-1 mRNA and protein expression(P<0.05);compared with the ox-LDL group, polyinosinic acid group and bezafibrate group could decrease LOX-1 mRNA and protein expression(P<0.05); compared with the bezafibrate group, polyinosinic acid and bezafibrate group could obviously decrease LOX-1 mRNA and protein expression(P<0.01); (2) Compared with the control group,ox-LDL could obviously decrease eNOS mRNA and protein expression(P<0.05);compared with the ox-LDL group, polyinosinic acid group and bezafibrate group could increase eNOS mRNA and protein expression(P<0.05); compared with the bezafibrate group, polyinosinic acid and bezafibrate group could obviously increase eNOS mRNA and protein expression(P<0.01).Conclusions: ox-LDL could decrease the expression of eNOS, ox-LDL could increase the expression of LOX-1, with injured the endothelial cells . Bezafibrate can increase the expression of eNOS, bezafibrate may increase the expression of eNOS ,which were participated by the action of LOX-1 , and may though inhibition LOX-1 in the development of arteriosclerosis.