Sulforaphane protects human umbilical vein endothelial cells from oxidative stress via the miR‑34a/SIRT1 axis by upregulating nuclear factor erythroid‑2‑related factor 2

Li,Tao; Pang,Qi; Liu,Yongbin; Bai,Ming; Peng,Yu; Zhang,Zheng

doi:10.3892/etm.2021.9617

Sulforaphane protects human umbilical vein endothelial cells from oxidative stress via the miR‑34a/SIRT1 axis by upregulating nuclear factor erythroid‑2‑related factor 2

Authors:
- Tao Li
- Qi Pang
- Yongbin Liu
- Ming Bai
- Yu Peng
- Zheng Zhang
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Affiliations: Department of Cardiology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Traditional Chinese Medicine, The Gansu Gem Flower Hospital, Lanzhou, Gansu 730000, P.R. China, Department of Cardiology, The Gansu Gem Flower Hospital, Lanzhou, Gansu 730000, P.R. China
Published online on: January 7, 2021 https://doi.org/10.3892/etm.2021.9617
Article Number: 186
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Oxidative stress‑induced vascular endothelial cell dysfunction serves an essential role in the initiation and development of atherosclerosis. Sulforaphane (SFN), a naturally occurring antioxidant, has previously demonstrated to exert protective effects on the endothelium against oxidative stress. However, further studies are required to determine its underlying molecular mechanism prior to clinical application. Accumulating evidence suggests that alterations in the microRNA (miRNA/miR)‑34a/sirtuin‑1 (SIRT1) axis occur with oxidative stress. Therefore, the present study aimed to investigate if SFN exerts a protective role against oxidative stress in vascular endothelial cells through regulation of the miR‑34a/SIRT1 axis. Human umbilical vein endothelial cells (HUVECs) were treated with H₂O₂ in the presence or absence of SFN pretreatment. Cell viability and apoptosis were analyzed using CellTiter‑Blue and flow cytometry, respectively. Reverse transcription‑quantitative PCR and western blot analyses were performed to determine changes in the expression levels of miR‑34a and SIRT1. The expression levels of miR‑34a and SIRT1 were artificially regulated following transfection with miR‑34a mimic and inhibitor or SIRT1expression plasmid and small interfering RNA, respectively. Subsequently, the effect of the expression changes of miR‑34 and SIRT1 on oxidative stress‑induced cell injury was investigated. Dual‑luciferase reporter assay was used to confirm the targeted binding of miR‑34a to SIRT1. SFN was found to ameliorate cellular damage caused by H₂O₂ and inhibited intracellular reactive oxygen species production. In addition, miR‑34a upregulation was accompanied with reduced SIRT1 expression in HUVECs, following H₂O₂ treatment. miR‑34a was revealed to directly target SIRT1 by binding to its 3'‑untranslated region. Down‑regulation of miR‑34a and up‑regulation of SIRT1 increased the survival of HUVECs under oxidative stress. Taken together, the results of the present study suggest that SFN may protect HUVECs from oxidative stress by inducing changes in the miR‑34a/SIRT1 axis via upregulation of nuclear factor erythroid‑2‑related factor 2 expression.

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