Exosomes Produced By HIF-1α Modified ADMSCs Can Improve The Dysfunction And Inflammation Of HUVECs Induced By Hypoxia

Objective:To investigate the effect of exosomes(EXOs)produced by adipose mesenchymal stem cells(ADMSCs)modified by Hypoxia inducible factor-1α(HIF-1α)on the dysfunction and inflammatory response of human umbilical vein endothelial cells(HUVECs)induced by hypoxia,and explore its possible molecular mechanism.Methods:HUVECs cultured were divided into normoxia Vector-exos group,normoxia HIF-1α-exos group,hypoxia Vector-exos group and hypoxia HIF-1α-exos group.Cell proliferation was detected by CCK8 assay.Annexin V-FITC/PI double staining was used to detect apoptosis.Transwell experiment was used to evaluate migration ability;The ability of tube formation was observed by angiogenesis experiment.ELISA was used to detect the secretion of IL-10,IL-6,VEGF and MCP-1.Western Blot was used to detect the expression of HIF-1α,SIRT-3,SDF-1α,VEGF,Rac1 and Rac2 in hypoxia Vector-exos group and hypoxia HIF-1α-exos group.HUVECs were divided into control group and si SIIRT3 group,and the two groups of cells were co-cultured with HIF-1α-exos under hypoxia conditions.The same method was used to detect cell proliferation,apoptosis,migration ability,ability of tube formation and cytokines secretion and the expression of related proteinsResults:Compared with Vector-exos,HIF-1α-exos increased the proliferation activity of HUVECs under hypoxia(P<0.01),inhibition of apoptosis(P<0.01),promoting cell migration(P<0.01)and tube formation(P<0.01),inhibition of IL-6 and MCP-1 expression(P<0.01),the release of VEGF and IL-10 increased(P<0.01).si SITR3 inhibited the effects of HIF-1α-exos on the proliferation,migration and inflammatory factors of HUVECs.Conclusion:HIF-1α-exos promotes the proliferation,tube formation and migration of HUVECs under hypoxia,and inhibits the release of inflammatory factors.Its molecular mechanism may be through up-regulation of SIRT3.