Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Chen,Jianfang; Zhang,Wei; Xu,Qing; Zhang,Jihua; Chen,Wei; Xu,Zhengrong; Li,Chaosheng; Wang,Zhenhua; Zhang,Yao; Zhen,Yulan; Feng,Jianqiang; Chen,Jun; Chen,Jingfu

doi:10.3892/ijmm.2018.3507

Ang-(1-7) protects HUVECs from high glucose-induced injury and inflammation via inhibition of the JAK2/STAT3 pathway

Authors:
- Jianfang Chen
- Wei Zhang
- Qing Xu
- Jihua Zhang
- Wei Chen
- Zhengrong Xu
- Chaosheng Li
- Zhenhua Wang
- Yao Zhang
- Yulan Zhen
- Jianqiang Feng
- Jun Chen
- Jingfu Chen
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Affiliations: Guangdong Medical University, Zhanjiang, Guangdong 524023, P.R. China, Department of Cardiology, Huangpu Division of The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510700, P.R. China, Department of Endocrinology, Shanxian Central Hospital of Shandong Province, Shanxian, Shangdong 274300, P.R. China, Department of Cardiology, The People's Hospital of Baoan Shenzhen, Shenzhen, Guangdong 518100, P.R. China, Department of Oncology, The Third People's Hospital of Dongguan City, Dongguan, Guangdong 523326, P.R. China, Department of Physiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Cardiovascular Medicine and Dongguan Cardiovascular Institute, The Third People's Hospital of Dongguan City, Dongguan, Guangdong 523326, P.R. China
Published online on: February 22, 2018 https://doi.org/10.3892/ijmm.2018.3507
Pages: 2865-2878

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Abstract

Angiotensin (Ang)‑1‑7, which is catalyzed by angiotensin‑converting enzyme 2 (ACE2) from angiotensin‑II (Ang‑II), exerts multiple biological and pharmacological effects, including cardioprotective effects and endothelial protection. The Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway has been demonstrated to be involved in diabetes‑associated cardiovascular complications. The present study hypothesized that Ang‑(1‑7) protects against high glucose (HG)‑induced endothelial cell injury and inflammation by inhibiting the JAK2/STAT3 pathway in human umbilical vein endothelial cells (HUVECs). HUVECs were treated with 40 mmol/l glucose (HG) for 24 h to establish a model of HG‑induced endothelial cell injury and inflammation. Protein expression levels of p‑JAK2, t‑JAK2, p‑STAT3, t‑STAT3, NOX‑4, eNOS and cleaved caspase‑3 were tested by western blotting. CCK‑8 assay was performed to assess cell viability of HUVECs. Apoptotic cell death was analyzed by Hoechst 33258 staining. Mitochondrial membrane potential (MMP) was obtained using JC‑1. Superoxide dismutase (SOD) activity was tested by SOD assay kit. Interleukin (IL)‑1β, IL‑10, IL‑12 and TNF‑α levels in culture media were tested by ELISA. The findings demonstrated that exposure of HUVECs to HG for 24 h induced injury and inflammation. This injury and inflammation were significantly ameliorated by pre‑treatment of cells with either Ang‑(1‑7) or AG490, an inhibitor of the JAK2/STAT3 pathway, prior to exposure of the cells to HG. Exposure of the cells to HG also increased the phosphorylation of JAK2/STAT3 (p‑JAK2 and p‑STAT3). Increased activation of the JAK2/STAT3 pathway was attenuated by pre‑treatment with Ang‑(1‑7). To the best of our knowledge, the findings from the present study provided the first evidence that Ang‑(1‑7) protects against HG‑induced injury and inflammation by inhibiting activation of the JAK2/STAT3 pathway in HUVECs.

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