| Abstract: | Previous reports have suggested that Ang-(1-7) may have a protective effect in endothelial cells against highglucose (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-1β and Heme oxygenase-1 (HO-1) pathways contribute to the protection ofAng-(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 glucoseconcentrations 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-1β production induced by HG. Ofnote, HUVECs previously treated with Ang-(1-7) (2 μM) for 30 min before being exposed to HG concentrationssignificantly ameliorated the HG-increased in p-p65 and IL-1β expression; whereas obviously up-regulated the level ofHO-1, along with inhibition of oxidative stress, inflammation, and the HG-induced cytotoxicity. Importantly, whenHUVECs were previously treated either with PDTC or IL-1Ra for 30 min before being exposed to HG, it significantlyprevented damages caused by high glucose concentrations mentioned above, while the treatment of HO-1 inhibitorSn-protoporphyrin (SnPP) before exposure to both HG and Ang-(1-7) significantly blocked the protective effectexerted by Ang-(1-7) on endothelial cells against injuries induced by HG mentioned above. To conclude, the data ofthis study showed that activation and inhibition of the NF-κB-IL-1β pathway and HO-1 pathway may constitute animportant defense mechanism against endothelial cell damage caused by HG concentrations. We additionally gavenew evidence showing that exogenous Ang-(1-7) exerts a protective effect on HUVECs against the HG-induced cellinjury via the inhibition and the activation of the NF-κB-IL-1β pathway and the HO-1 pathway, respectively. |
