Bazedoxifene activates the angiotensin II‑induced HUVEC hypertension model by targeting SIRT1

Yu,Qian; Zhao,Jin; Liu,Baotang

doi:10.3892/etm.2021.11043

Bazedoxifene activates the angiotensin II‑induced HUVEC hypertension model by targeting SIRT1

Authors:
- Qian Yu
- Jin Zhao
- Baotang Liu
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Affiliations: Department of Cardiovascular Medicine, Sichuan Chengdu Fifth People's Hospital, Chengdu, Sichuan 611130, P.R. China, Department of Cardiovascular Surgical, Affiliated Hospital of Weifang Medical University, Weifang, Shadong 261031, P.R. China
Published online on: December 7, 2021 https://doi.org/10.3892/etm.2021.11043
Article Number: 120
Copyright: © Yu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The shift in vascular function to vasoconstriction, pro‑inflammatory state, oxidative stress and carbon monoxide deficiency may to endothelial dysfunction and injury, which is the key event in hypertension. Estrogen receptor modulators play a protective role in blood vessels. The present study aimed to investigate the effect of bazedoxifene, a selective estrogen receptor modulator, on human umbilical vein endothelial cells (HUVECs) and its potential underlying mechanism of action. The present study treated endothelial cells with different concentrations of bazedoxifene and determined cell viability using Cell Counting Kit‑8 to screen for the optimal working concentration of bazedoxifene. Subsequently, an angiotensin II (AngII)‑induced vascular endothelial cell model was established to observe the effect of bazedoxifene on AngII‑induced endothelial cells. The concentrations of nitric oxide (NO) and reactive oxygen species (ROS) were detected using NO and ROS kits, respectively. The protein expression of sirtuin 1 (SIRT1), oxidative stress‑related proteins and apoptosis‑related proteins was detected using western blotting, and apoptosis was detected using a TUNEL assay. The results demonstrated that bazedoxifene promoted AngII‑induced HUVEC viability, reduced the expression of stress‑related proteins and inhibited apoptosis. Furthermore, bazedoxifene activated SIRT1 to promote the proliferation and inhibit the oxidative stress and apoptosis of AngII‑induced HUVECs. These findings suggested that bazedoxifene could effectively promote AngII‑induced HUVEC proliferation and inhibit cell apoptosis and oxidative stress. In addition, bazedoxifene protected HUVEC dysfunction induced by AngII by targeting the activation of SIRT1. In summary, bazedoxifene could improve the protective role against hypertension induced by AngII.

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