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MicroRNA-24 inhibits the oxidative stress induced by vascular injury by activating the Nrf2/Ho-1 signaling pathway

  • Author Footnotes
    1 These authors contribute equally to this study.
    Jing Zhang
    Footnotes
    1 These authors contribute equally to this study.
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
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  • Author Footnotes
    1 These authors contribute equally to this study.
    Wanyin Cai
    Footnotes
    1 These authors contribute equally to this study.
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Zhixing Fan
    Affiliations
    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Chaojun Yang
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Wei Wang
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Mengting Xiong
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Cong Ma
    Affiliations
    Central Laboratory, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Jian Yang
    Correspondence
    Corresponding author. Department of Cardiology, the First College of Clinical Medical Sciences, Institute of Cardiovascular Diseases, China Three Gorges University, Yichang, 443000, Hubei Province, China.
    Affiliations
    Department of Cardiology, The First College of Clinical Medical Science, China Three Gorges University & Yichang Central People's Hospital, Yichang, 443003, China

    Yichang Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contribute equally to this study.

      Highlights

      • MiR-24 up-regulation inhibits HG-stimulated oxidative stress of VSMCs.
      • MiR-24 up-regulation promotes reendothelialization in balloon-injured diabetic rats.
      • MiR-24 up-regulation inhibits Ogt and keap1 expression, and promotes Nrf2 and Ho-1 expression.

      Abstract

      Background and aims

      The process of endothelial repair in diabetic patients after stent implantation was significantly delayed compared with that in non-diabetic patients, and oxidative stress is increasingly considered to be relevant to the pathogenesis of diabetic endothelial repair. However, the mechanisms linking diabetes and reendothelialization after vascular injury have not been fully elucidated. The aim of this study was to evaluate the effect of microRNA-24 (miR-24) up-regulation in delayed endothelial repair caused by oxidative stress after balloon injury in diabetic rats.

      Methods

      In vitro, vascular smooth muscle cells (VSMCs) isolated from the thoracic aorta were stimulated with high glucose (HG) after miR-24 recombinant adenovirus (Ad-miR-24-GFP) transfection for 3 days. In vivo, diabetic rats induced using high-fat diet (HFD) and low-dose streptozotocin (30 mg/kg) underwent carotid artery balloon injury followed by Ad-miR-24-GFP transfection for 20 min.

      Results

      The expression of miR-24 was decreased in HG-stimulated VSMCs and balloon-injured carotid arteries of diabetic rats, which was accompanied by increased expression of Ogt and Keap1 and decreased expression of Nrf2 and Ho-1. Up-regulation of miR-24 suppressed VSMC oxidative stress induced by HG in vitro, and miR-24 up-regulation promoted reendothelialization in balloon-injured diabetic rats. The underlying mechanism was related to the activation of the Nrf2/Ho-1 signaling pathway, which subsequently suppressed intracellular reactive oxidative species (ROS) production and malondialdehyde (MDA) and NADPH oxidase (Nox) activity, and to the restoration of Sod and Gsh-px activation.

      Conclusions

      The up-regulation of miR-24 significantly promoted endothelial repair after balloon injury through inhibition of oxidative stress by activating the Nrf2/Ho-1 signaling pathway.

      Graphical abstract

      Keywords

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