Objective:To investigate the molecular mechanism and function of long non-coding RNA nuclear paraspeckle assembly transcript 1(lncRNA NEAT1)in oxidative low-density lipoprotein(ox-LDL)-induced vascular endothelial cell injury.Methods:Blood samples of healthy people and atherosclerosis(AS)patients were collected and serum lncRNA NEAT1,micrornA-424-5p(miR-424-5p)and ETS domain protein 4(ELK4)mRNA expression levels were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction(qRT-PCR).Human umbilical vein endothelial cells(HUVEC)were cultured in vitro,and the expressions of lncRNA NEAT1,miR-424-5p and ELK4 were detected by qRT-PCR and Western Blot.Cell counting kit(CCK-8)and Annexin V-FITC/PI method were used to detect the proliferation and apoptosis of HUVEC cells.Lactate dehydrogenase(LDH)release,tumor necrosis factor-α(TNF-α)and interleukin-1β contents,lipoprotein phospholipase A2(Lp-PLA2)and C-reactive protein(CRP)levels in HUVEC were determined by enzyme-linked immunosorbent assay(ELISA).Targeting interactions between lncRNA NEAT1,miR-424-5p and ELK4 were determined by dual luciferase reporter genes.Animal experiments were performed to evaluate the role of lncRNA NEAT1 in the progression of AS in vivo.Results:lncRNA NEAT1 was significantly up-regulated in AS patients'serum and ox-LDL-induced HUVECs(P<0.05).Silencing of lncRNA NEAT1 attenuated ox-LDL-induced cytotoxicity,reduced Lp-PLA2 and CRP levels,and reduced abnormal lipid secretion in ApoE-/-mice(P<0.05).miR-424-5p mediated lncRNA NEAT1 in regulating ox-LDL-induced HUVEC injury,and ELK4 was the direct target of miR-424-5p(P<0.05).Inhibition of miR-424-5p or overexpression of ELK4 reversed the effect of lncRNA NEAT1 silencing on ox-LDL-induced HUVEC cell damage(P<0.05).Conclusion:Silencing lncRNA NEAT1 protects HUVEC from ox-LDL-triggered cytotoxicity and reduces Lp-PLA2 and CRP levels,in part by regulating the miR-424-5p/ELK4 axis.
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