Mechanism of Bromodomain 4 Aggravates High Glucose-Induced Endothelial Cell Injury
SUN Yunlong
WANG Xijia
MENG Zhe
GAO Lu
Abstract：Objective To investigate the effect and mechanism of Bromodomain 4(BRD4)on high glucose-induced vascular endothelial cell injury.Methods Human umbilical vein endothelial cells(HUVECs)were cultured,and the cells were divided into 4 groups:control group,high glucose stimulation group(HG),BRD4 silencing group(BRD4 siRNA group),and BRD4 silencing+HG group.ELISA was used to detect the secretion of inflammatory cytokines in each group.And kits were used to detect the levels of intracellular reactive oxygen species(ROS).Kits were used to detect the activities of superoxide dismutase 2(SOD2)and Gpx,and malondialdehyde(MDA)level.Nitric oxide(NO)content was detected by NO detection kit.Nuclear factor-E2-related factor 2(NRF2)expression and nuclear translocation were detected by immunofluorescence staining.Results There were no statistically significant differences between the control group and the BRD4 siRNA group in levels of pro-inflammatory factors,ROS,MDA,NO,activities of antioxidant enzymes SOD2 and Gpx,cell activity,number of cell apoptosis,NRF2 expression,and nuclear translocation level(P＞0.05).The levels of pro-inflammatory factors,ROS,and MDA in the HG group and BRD4 siRNA+HG group were higher than those in the control group,while the levels of antioxidant enzymes SOD2,Gpx,NO,cell activity,NRF2 expression,and nuclear translocation were lower than those in the control group.In addition,the levels of pro-inflammatory factors,ROS,and MDA in the BRD4 siRNA+HG group were lower than those in the HG group,while the levels of SOD2,Gpx,NO,cell activity,cell NRF2 expression,and nuclear translocation were higher than those in the HG group(P＜0.05).The number of apoptotic cells in the HG group and BRD4 siRNA+HG group was higher than that in the control group.Compared with the HG group,the number of apoptotic cells in the BRD4 siRNA+HG group decreased(P＜0.05).Conclusion BRD4 aggravates high glucose induced endothelial cell injury by inhibiting nuclear translocation of NRF2.BRD4 may be involved in the occurrence and development of complications of diabetes.
Keywords：endothelial cellshyperglycemiaBromodomain 4oxidative stressNF-E2-related factor 2
Publication Date：2023-11-30
Online Publishing Date：2026-09-12(First online date of this platform, not the publication date of the document)
Pages：5( 4033-4037 )