MicroRNA-140-5p aggravates hypertension and oxidative stress of atherosclerosis via targeting Nrf2 and Sirt2

Liu,Qing‑Quan; Ren,Ke; Liu,Su‑Hong; Li,Wei‑Min; Huang,Chang‑Jun; Yang,Xiu‑Hui

doi:10.3892/ijmm.2018.3996

MicroRNA-140-5p aggravates hypertension and oxidative stress of atherosclerosis via targeting Nrf2 and Sirt2

Authors:
- Qing‑Quan Liu
- Ke Ren
- Su‑Hong Liu
- Wei‑Min Li
- Chang‑Jun Huang
- Xiu‑Hui Yang
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Affiliations: Department of General Surgery II, Central Hospital of Luohe, Luohe, Henan 462000, P.R. China, Department of Vascular Surgery, The Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, P.R. China
Published online on: November 26, 2018 https://doi.org/10.3892/ijmm.2018.3996
Pages: 839-849
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In the present study, the function of microRNA (miR)‑140‑5p on oxidative stress in mice with atherosclerosis was investigated. A reverse transcription‑quantitative polymerase chain reaction assay was used to determine the expression of miR‑140‑5p. Oxidative stress kits and reactive oxygen species (ROS) kits were used to analyze alterations in oxidative stress and ROS levels. The alterations in protein expression were determined using western blot analysis and an immunofluorescence assay. miR‑140‑5p expression was increased in mice with atherosclerosis with hypertension. Consistently, miR‑140‑5p expression was also increased in mice with atherosclerosis. Upregulation of miR‑140‑5p increased oxidative stress and ROS levels by suppressing the protein expression of nuclear factor erythroid 2‑related factor 2 (Nrf2), sirtuin 2 (Sirt2), Kelch‑like enoyl‑CoA hydratase‑associated protein 1 (Keap1) and heme oxygenase 1 (HO‑1) in vitro. By contrast, downregulation of miR‑140‑5p decreased oxidative stress and ROS levels by activating the protein expression of Nrf2, Sirt2, Keap1 and HO‑1 in vitro. Sirt2 agonist or Nrf2 agonist inhibited the effects of miR‑140‑5p on oxidative stress in vitro. Collectively, these results suggested that miR‑140‑5p aggravated hypertension and oxidative stress of mice with atherosclerosis by targeting Nrf2 and Sirt2.

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