miR-874-5p在冠心病内皮损伤中的作用OA

To investigate the expression of miR-874-5p in patients with coronary heart disease and its effects on endothelial cell function under oxidative stress,and to preliminarily explore the underlying molecular mechanism.Peripheral blood leukocytes were obtained from 80 patients diagnosed with coronary heart disease and 80 healthy individuals.The expression of miR-874-5p was determined by real-time quantitative polymerase chain reaction(RT-qPCR),and its correlations with clinical indicators and diagnostic value were analyzed.Human umbilical vein endothelial cells(HUVECs)were treated with hydrogen peroxide(H2O2)to establish an oxidative stress model.Transient transfection was performed to construct miR-874-5p overexpression and knockdown cell models.Cell proliferation,migration,reactive oxygen species,malondialdehyde,superoxide dismutase activity,glutathione system,and apoptosis were evaluated.Transcriptome sequencing combined with RT-qPCR and western blotting was used to identify and validate the downstream target gene of miR-874-5p.The expression of miR-874-5p in peripheral blood leukocytes was significantly reduced in patients with coronary heart disease compared with healthy controls(P<0.0001).Its expression was negatively correlated with total cholesterol,triglycerides,and low-density lipoprotein cholesterol.Receiver operating characteristic curve analysis showed that the area under the curve for diagnosing coronary heart disease was 0.88(P<0.0001).An oxidative stress model was successfully established by treatment with 500 μmol/L H2O2 for 24 h.Overexpression of miR-874-5p inhibited the proliferation and migration of HUVECs,decreased the levels of reactive oxygen species and malondialdehyde,increased superoxide dismutase activity and the ratio of reduced glutathione to oxidized glutathione,and alleviated apoptosis.In contrast,knockdown of miR-874-5p produced opposite effects.Transcriptome sequencing and bioinformatics analysis suggested that tumor necrosis factor ligand superfamily member 10 was a potential downstream target gene of miR-874-5p,which was further confirmed by RT-qPCR and western blotting.miR-874-5p was lowly expressed in patients with coronary heart disease and had potential auxiliary diagnostic value.It may exert protective effects on endothelial cells by attenuating oxidative stress and apoptosis,and this mechanism may be associated with the targeted regulation of tumor necrosis factor ligand superfamily member 10.