Evidence map›Paper›PMID 28882869›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2018

Extracellular Vesicles Secreted by Atherogenic Macrophages Transfer MicroRNA to Inhibit Cell Migration.

My-Anh Nguyen, Denuja Karunakaran, Michèle Geoffrion, Henry S Cheng, Kristofferson Tandoc, Ljubica Perisic Matic, Ulf Hedin, Lars Maegdefessel, Jason E Fish, Katey J Rayner

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PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
153citing papers in PubMed, 2 pooled it
8.6field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

153 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.

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93 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 3 countries.

My-Anh NguyenFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Denuja KarunakaranFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Michèle GeoffrionFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Henry S ChengFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Kristofferson TandocFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Ljubica Perisic MaticFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Ulf HedinFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Lars MaegdefesselFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Jason E FishFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.).
Katey J RaynerFrom the University of Ottawa Heart Institute, Ontario, Canada (M.-A.N., D.K., M.G., K.T., K.J.R.); Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario, Canada (M.-A.N., K.J.R.); Toronto General Research Hospital Institute, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada (H.S.C., J.E.F.); Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden (L.P.M., U.H.); and Department of Vascular and Endovascular Surgery, Technical University Munich, Germany (L.M.). krayner@ottawaheart.ca.
University of Ottawa · CAKarolinska Institutet · SETechnical University of Munich · DE

Funding

miR-33 Pathway Inhibition for Improving HDL FunctionalityR01HL119047 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOORE, KATHRYN J, RAYNER, KATEY · 2015 to 2018
$1.9M
CIHR FND148448NHLBI NIH HHS R01 HL119047
6 · The paper itself

Abstract

objectiveDuring inflammation, macrophages secrete vesicles carrying RNA, protein, and lipids as a form of extracellular communication. In the vessel wall, extracellular vesicles (EVs) have been shown to be transferred between vascular cells during atherosclerosis; however, the role of macrophage-derived EVs in atherogenesis is not known. Here, we hypothesize that atherogenic macrophages secrete microRNAs (miRNAs) in EVs to mediate cell-cell communication and promote proinflammatory and proatherogenic phenotypes in recipient cells. APPROACH AND

resultsWe isolated EVs from mouse and human macrophages treated with an atherogenic stimulus (oxidized low-density lipoprotein) and characterized the EV miRNA expression profile. We confirmed the enrichment of miR-146a, miR-128, miR-185, miR-365, and miR-503 in atherogenic EVs compared with controls and demonstrate that these EVs are taken up and transfer exogenous miRNA to naive recipient macrophages. Bioinformatic pathway analysis suggests that atherogenic EV miRNAs are predicted to target genes involved in cell migration and adhesion pathways, and indeed delivery of EVs to naive macrophages reduced macrophage migration both in vitro and in vivo. Inhibition of miR-146a, the most enriched miRNA in atherogenic EVs, reduced the inhibitory effect of EVs on macrophage migratory capacity. EV-mediated delivery of miR-146a repressed the expression of target genes IGF2BP1 (insulin-like growth factor 2 mRNA-binding protein 1) and HuR (human antigen R or ELAV-like RNA-binding protein 1) in recipient cells, and knockdown of IGF2BP1 and HuR using short interfering RNA greatly reduced macrophage migration, highlighting the importance of these EV-miRNA targets in regulating macrophage motility.

conclusionsEV-derived miRNAs from atherogenic macrophages, in particular miR-146a, may accelerate the development of atherosclerosis by decreasing cell migration and promoting macrophage entrapment in the vessel wall.

Indexed as

Cell MovementAnimalsAtherosclerosisCoculture TechniquesDisease Models, AnimalELAV-Like Protein 1Extracellular VesiclesGene Expression RegulationHumansMacrophages, PeritonealMiceMice, Inbred C57BLMice, Knockout, ApoEMicroRNAsRAW 264.7 CellsRNA-Binding ProteinsCRD-BP protein, mouseElavl1 protein, mouseELAV-Like Protein 1MicroRNAsMirn146 microRNA, mouseRNA-Binding Proteinsatherosclerosisexosomesextracellular vesiclesmacrophagemicroRNAmigration

Identifiers

PMID28882869
PMCPMC5884694
OpenAlexW2750610314

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.