title: HDL-transferred microRNA-223 regulates ICAM-1 expression in endothelial cells.
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.
authors.affiliation: 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].
authors.forename: Fatiha
authors.initials: F
authors.lastname: Tabet
authors.affiliation: 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].
authors.forename: Kasey C
authors.initials: KC
authors.lastname: Vickers
authors.affiliation: 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.
authors.forename: Luisa F
authors.initials: LF
authors.lastname: Cuesta Torres
authors.affiliation: Division of Cardiovascular Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors.forename: Carrie B
authors.initials: CB
authors.lastname: Wiese
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA.
authors.forename: Bassem M
authors.initials: BM
authors.lastname: Shoucri
authors.affiliation: Université de Nantes, Faculté de Médecine, Laboratoire Inserm U957, Nantes, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.affiliation: Lipid Research Group, The Heart Research Institute, New South Wales 2042, Australia.
authors.forename: Claire
authors.initials: C
authors.lastname: Catherinet
authors.affiliation: Centre for Vascular Research, The University of New South Wales, Sydney, New South Wales 2052, Australia.
authors.forename: Leonel
authors.initials: L
authors.lastname: Prado-Lourenco
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Levin
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA.
authors.forename: Seth
authors.initials: S
authors.lastname: Thacker
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA.
authors.forename: Praveen
authors.initials: P
authors.lastname: Sethupathy
authors.affiliation: 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.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.affiliation: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20814-9692, USA.
authors.forename: Alan T
authors.initials: AT
authors.lastname: Remaley
authors.affiliation: 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.
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000328:Adult; D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D064368:Healthy Volunteers; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: D018799:Intercellular Adhesion Molecule-1; D008075:Lipoproteins, HDL; D035683:MicroRNAs; C525067:MIR223, human