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HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells

Author

Listed:
  • Fatiha Tabet

    (Centre for Vascular Research, The University of New South Wales
    Lipid Research Group, The Heart Research Institute
    Faculty of Medicine, University of Sydney)

  • Kasey C. Vickers

    (National Heart, Lung and Blood Institute, National Institutes of Health
    Vanderbilt University School of Medicine)

  • Luisa F. Cuesta Torres

    (Centre for Vascular Research, The University of New South Wales
    Lipid Research Group, The Heart Research Institute)

  • Carrie B. Wiese

    (Vanderbilt University School of Medicine)

  • Bassem M. Shoucri

    (National Heart, Lung and Blood Institute, National Institutes of Health)

  • Gilles Lambert

    (Université de Nantes, Faculté de Médecine, Laboratoire Inserm U957)

  • Claire Catherinet

    (Lipid Research Group, The Heart Research Institute)

  • Leonel Prado-Lourenco

    (Centre for Vascular Research, The University of New South Wales)

  • Michael G. Levin

    (National Heart, Lung and Blood Institute, National Institutes of Health)

  • Seth Thacker

    (National Heart, Lung and Blood Institute, National Institutes of Health)

  • Praveen Sethupathy

    (University of North Carolina)

  • Philip J. Barter

    (Centre for Vascular Research, The University of New South Wales
    Lipid Research Group, The Heart Research Institute
    Faculty of Medicine, University of Sydney)

  • Alan T. Remaley

    (National Heart, Lung and Blood Institute, National Institutes of Health)

  • Kerry-Anne Rye

    (Centre for Vascular Research, The University of New South Wales
    Lipid Research Group, The Heart Research Institute
    Faculty of Medicine, University of Sydney)

Abstract

High-density lipoproteins (HDL) have many biological functions, including reducing endothelial activation and adhesion molecule expression. We recently reported that HDL transport and deliver functional microRNAs (miRNA). Here we show that HDL suppresses expression of intercellular adhesion molecule 1 (ICAM-1) through the transfer of miR-223 to endothelial cells. After incubation of endothelial cells with HDL, mature miR-223 levels are significantly increased in endothelial cells and decreased on HDL. However, miR-223 is not transcribed in endothelial cells and is not increased in cells treated with HDL from miR-223−/− mice. HDL inhibit ICAM-1 protein levels, but not in cells pretreated with miR-223 inhibitors. ICAM-1 is a direct target of HDL-transferred miR-223 and this is the first example of an extracellular miRNA regulating gene expression in cells where it is not transcribed. Collectively, we demonstrate that HDL’s anti-inflammatory properties are conferred, in part, through HDL-miR-223 delivery and translational repression of ICAM-1 in endothelial cells.

Suggested Citation

  • Fatiha Tabet & Kasey C. Vickers & Luisa F. Cuesta Torres & Carrie B. Wiese & Bassem M. Shoucri & Gilles Lambert & Claire Catherinet & Leonel Prado-Lourenco & Michael G. Levin & Seth Thacker & Praveen , 2014. "HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4292
    DOI: 10.1038/ncomms4292
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