Ang-(1-7) exerts anti-inflammatory and antioxidant activities on high glucose-induced injury by prohibiting NF-κB-IL-1β and activating HO-1 pathways in HUVECs

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-1β and 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-1β production induced by HG. Of note, HUVECs previously treated with Ang-(1-7) (2 μM) for 30 min before being exposed to HG concentrations significantly ameliorated the HG-increased in p-p65 and IL-1β expression; 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-1β pathway 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-1β pathway and the HO-1 pathway, respectively.