Carvedilol may attenuate liver cirrhosis by inhibiting angiogenesis through the VEGF-Src-ERK signaling pathway

World Journal of Gastroenterology : WJG
Qian DingChun-Qing Zhang

Abstract

To investigate the effect of carvedilol on angiogenesis and the underlying signaling pathways. The effect of carvedilol on angiogenesis was examined using a human umbilical vascular endothelial cell (HUVEC) model. The effect of carvedilol on cell viability was measured by CCK8 assay. Flow cytometry was used to assess the effect of carvedilol on cell cycle progression. Cell migration, transwell migration and tube formation assays were performed to analyze the effect of carvedilol on HUVEC function. Vascular endothelial growth factor (VEGF) induced activation of HUVECs, which were pretreated with different carvedilol concentrations or none. Western blot analysis detected the phosphorylation levels of three cell signaling pathway proteins, VEGFR-2, Src, and extracellular signal-regulated kinase (ERK). The specific Src inhibitor PP2 was used to assess the role of Src in the VEGF-induced angiogenic pathway. Carvedilol inhibited HUVEC proliferation in a dose-dependent manner (IC50 = 38.5 mmol/L). The distribution of cells in the S phase decreased from 43.6% to 37.2%, 35.6% and 17.8% by 1, 5 and 10 μmol/L carvedilol for 24 h, respectively. Carvedilol (10 μmol/L) reduced VEGF-induced HUVEC migration from 67.54 ± 7.83 to 37.11 ± 3.533 (...Continue Reading

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Citations

Aug 9, 2016·Journal of Ethnopharmacology·Yan-Hui SunRen Zhang
Jan 28, 2017·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Wei-Jin ZhangQiao-Bing Huang
Sep 19, 2019·Circulation Journal : Official Journal of the Japanese Circulation Society·Maya AdachiIchiro Hisatome
Nov 3, 2020·Expert Review of Gastroenterology & Hepatology·Hui Li

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