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

Biocell

article

FEI CHENG¹  YIQIAN DING²  QING XU³  WEI ZHANG³  YULAN ZHEN⁴  JING LIU⁵  SHICHENG LI¹  CHANG TU¹  GUOHUA LAI¹  JUN LAN¹  JINGFU CHEN¹ 

[1] Department of Cardiovascular Medicine, Dongguan Songshan Lake Center Hospital, Dongguan Cardiovascular Institute, Dongguan Shilong People’s Hospital Affiliated to Southern Medical University;Department of Ultrasound, The First Affiliated Hospital, Sun Yat-sen University;Department of Cardiology, Huangpu Division of the First Affiliated Hospital, Sun Yat-sen University;Department of Oncology, Dongguan Third People’s Hospital;Second Ward of Internal Medicine, Dongguan Eighth People’s Hospital, Dongguan Children’s Hospital

关键词: Angiotensin-(1-7);    High glucose;    Human umbilical vein endothelial cells;    NF-κB;    IL-1β;    HO-1;   

DOI  :  10.32604/biocell.2021.012901

学科分类：仪器

来源: Biocell

【 摘 要 】

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.

【 授权许可】

CC BY