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Nat Commun. 2014 Feb 28;5:3292. doi: 10.1038/ncomms4292.

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

Author information

1
1] Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales 2052, Australia [2] Lipid Research Group, The Heart Research Institute, New South Wales 2042, Australia [3] Faculty of Medicine, University of Sydney, Sydney New South Wales 2006, Australia [4].
2
1] National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA [2] Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA [3].
3
1] Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales 2052, Australia [2] Lipid Research Group, The Heart Research Institute, New South Wales 2042, Australia.
4
Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
5
National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA.
6
Université de Nantes, Faculté de Médecine, Laboratoire Inserm U957, Nantes, France.
7
Lipid Research Group, The Heart Research Institute, New South Wales 2042, Australia.
8
Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales 2052, Australia.
9
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA.
10
1] Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales 2052, Australia [2] Lipid Research Group, The Heart Research Institute, New South Wales 2042, Australia [3] Faculty of Medicine, University of Sydney, Sydney New South Wales 2006, Australia.

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.

PMID:
24576947
PMCID:
PMC4189962
DOI:
10.1038/ncomms4292
[Indexed for MEDLINE]
Free PMC Article
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