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

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.

Therapeutic blockade of inflammation in severe COVID-19 infection with intravenous N-acetylcysteine

“…In addition to epithelial, endothelial, and myocardial cells [ 30 , 31 ], ACE2 is expressed on T lymphocytes [ 32 ], macrophages [ 33 ], and hepatocytes [ [34] , [35] , [36] , [37] ]. ACE2 controls the expression of pro-inflammatory transcription factor Stat3 [ [38] , [39] , [40] , [41] , [42] , [43] ], which also modulates the production of reactive oxygen intermediates by complex I of the mitochondrial electron transport chain (ETC) [ 44 ]. ACE2 also attenuates signaling through mTORC1 [ [45] , [46] , [47] , [48] ] ( Fig.…”

<p>Luteolin Attenuates Atherosclerosis Via Modulating Signal Transducer And Activator Of Transcription 3-Mediated Inflammatory Response</p>

“…There is also evidence that inhibition of JAK2/STAT3 signal pathway might help prevent LPS-induced inflammation 32,33. Besides, inhibitors of the JAK2/STAT3 pathway have been shown to significantly ameliorate HG/AngII-induced inflammation 34,35. Cupric-ion-oxidized LDL (CuLDL), endothelial cell-oxidized LDL (ELDL) and oxLDL also induced the phosphorylation of JAK2, and then activated STAT3 36.…”

A novel peptide relieves endothelial cell dysfunction in preeclampsia by regulating the PI3K/mTOR/HIF1α pathway

“…The preliminary experiment indicated that untreated HUVECs completely formed tubular structures on the Matrigel after 6-8 h of incubation (data not shown). Thus, the tube formation of the HUVECs was observed using a bright-field microscope (magnification, x200) at 6-8 h, as also previously described (34)(35)(36). The branch number and length of the tubes were quantified using ImageJ software (v1.52a; National Institutes of Health).…”