Role Of RXRα In The Depression Of Atorvastatin On High-glucose-induced Oxidative Stress In Human Endothelial Cells

Object: To investige the effect of RXRα on high-glucose-induced oxidative stress inhuman endothelial cells and underlying mechanism.Methods: Human umbilical vein endothelial cells (HUVECs) were isolated fromhealthy umbilical cords and cultured. RXRα agonist (9-cis-RA) and RXRα antagonist(UVI3003) was used to pre-treat the cells. Reverse transcription and real-time PCRwere performed to determine the expression of the components of NADPH oxidase.ROS production was detected with flow cytometry and fluorescence microscopy.Lucigenin assay was used to measure the NADPH oxidase activity. The expression ofNADPH oxidase subunit Nox4, Nox2and p22phoxmRNA were detected by real-timePCR Activation of PKC were detected using immunoblotting. Action of RXRα wasdemonstrated using transfection of small interfering RNA and plasmid DNA．Results: RXRα agonist9-cis-RA could reduce high-glucose-induced oxidative stress,expression of Nox4, Nox2, and p22phoxand NADPH oxidase activation.9-cis-RA alsoinhibits high-glucose-induced PKC activation. Compared with9-cis-RA, RXRαantagonist UVI3003has the opposite effects on oxidative injury. Inhibition ofhigh-glucose-induced ROS and PKC phosphorylation by9-cis-RA was largelyimpaired when cells were transfected with RXRα siRNA, nevertheless, the effect ofUVI3003was significantly attenuated in HUVECs transfected with RXRα plasmid.Conclusion: RXRα might be implicated during the oxidative stress induced by highglucose in endothelial cells.