Previous reports have suggested that Ang-(1-7)may have a protective effect in endothelial cells against high glucose(HG)-induced cell injury thanks to a modulatory mechanism in the NF-κB signaling pathway.In this stu...Previous reports have suggested that Ang-(1-7)may have a protective effect in endothelial cells against high glucose(HG)-induced cell injury thanks to a modulatory mechanism in the NF-κB signaling pathway.In this study,we have examined whether NF-κB-IL-1βand Heme oxygenase-1(HO-1)pathways contribute to the protection of Ang-(1-7)against hyperglycemia-induced inflammation and oxidative stress in human umbilical vein endothelial cells(HUVECs).Our results indicate that time-varying exposures of HUVECs,from 1 h to 24 h,to high glucose concentrations result in an increased expression of phosphorylated(p)-p65 and HO-1 in a time-dependent manner.As an inhibitor of NF-κB,pyrrolidinedithiocarbamic acid(PDTC)suppressed IL-1βproduction induced by HG.Of note,HUVECs previously treated with Ang-(1-7)(2μM)for 30 min before being exposed to HG concentrations significantly ameliorated the HG-increased in p-p65 and IL-1βexpression;whereas obviously up-regulated the level of HO-1,along with inhibition of oxidative stress,inflammation,and the HG-induced cytotoxicity.Importantly,when HUVECs were previously treated either with PDTC or IL-1Ra for 30 min before being exposed to HG,it significantly prevented damages caused by high glucose concentrations mentioned above,while the treatment of HO-1 inhibitor Sn-protoporphyrin(SnPP)before exposure to both HG and Ang-(1-7)significantly blocked the protective effect exerted by Ang-(1-7)on endothelial cells against injuries induced by HG mentioned above.To conclude,the data of this study showed that activation and inhibition of the NF-κB-IL-1βpathway and HO-1 pathway may constitute an important defense mechanism against endothelial cell damage caused by HG concentrations.We additionally gave new evidence showing that exogenous Ang-(1-7)exerts a protective effect on HUVECs against the HG-induced cell injury via the inhibition and the activation of the NF-κB-IL-1βpathway and the HO-1 pathway,respectively.展开更多
基金supported by the Technology Planning Project of Huangpu District(201544-01)Medical Scientific Research Foundation of Guangdong Province(A2015287)+2 种基金Science and Technology Planning Project of Guangdong Province(2017ZC0474)Natural Science Foundation of Guangdong Province(2015A030313690)General Project of Dongguan City(Nos.201950715024922 and 2018507150241344).
文摘Previous reports have suggested that Ang-(1-7)may have a protective effect in endothelial cells against high glucose(HG)-induced cell injury thanks to a modulatory mechanism in the NF-κB signaling pathway.In this study,we have examined whether NF-κB-IL-1βand Heme oxygenase-1(HO-1)pathways contribute to the protection of Ang-(1-7)against hyperglycemia-induced inflammation and oxidative stress in human umbilical vein endothelial cells(HUVECs).Our results indicate that time-varying exposures of HUVECs,from 1 h to 24 h,to high glucose concentrations result in an increased expression of phosphorylated(p)-p65 and HO-1 in a time-dependent manner.As an inhibitor of NF-κB,pyrrolidinedithiocarbamic acid(PDTC)suppressed IL-1βproduction induced by HG.Of note,HUVECs previously treated with Ang-(1-7)(2μM)for 30 min before being exposed to HG concentrations significantly ameliorated the HG-increased in p-p65 and IL-1βexpression;whereas obviously up-regulated the level of HO-1,along with inhibition of oxidative stress,inflammation,and the HG-induced cytotoxicity.Importantly,when HUVECs were previously treated either with PDTC or IL-1Ra for 30 min before being exposed to HG,it significantly prevented damages caused by high glucose concentrations mentioned above,while the treatment of HO-1 inhibitor Sn-protoporphyrin(SnPP)before exposure to both HG and Ang-(1-7)significantly blocked the protective effect exerted by Ang-(1-7)on endothelial cells against injuries induced by HG mentioned above.To conclude,the data of this study showed that activation and inhibition of the NF-κB-IL-1βpathway and HO-1 pathway may constitute an important defense mechanism against endothelial cell damage caused by HG concentrations.We additionally gave new evidence showing that exogenous Ang-(1-7)exerts a protective effect on HUVECs against the HG-induced cell injury via the inhibition and the activation of the NF-κB-IL-1βpathway and the HO-1 pathway,respectively.
