Evidence map›Paper›PMID 26821945›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2016

Extracellular Vesicles Activate a CD36-Dependent Signaling Pathway to Inhibit Microvascular Endothelial Cell Migration and Tube Formation.

Devi Prasadh Ramakrishnan, Rula A Hajj-Ali, Yiliang Chen, Roy L Silverstein

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
4.4field-weighted citation impact, top 5% 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

38 citing papers in PubMed, 88 citations in OpenAlex.

  1. Article
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  5. Review
  6. Targeting Cysteine Oxidation in Thrombotic Disorders.Antioxidants (Basel, Switzerland) · 2024
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  18. Comprehensive phenotyping of endothelial cells using flow cytometry 2: Human.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2021
    Review
  19. Exosomes: Emerging Cell-Free Based Therapeutics in Dermatologic Diseases.Frontiers in cell and developmental biology · 2021
    Review
  20. The crosstalk: exosomes and lipid metabolism.Cell communication and signaling : CCS · 2020
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 3 institutions in 1 country.

Devi Prasadh RamakrishnanFrom the Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH (D.P.R.); Laboratory of Vascular Pathobiology, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI (D.P.R., Y.C., R.L.S.); Department of Rheumatologic and Immunologic Disease, Orthopedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, OH (R.A.H.-A.); and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI (R.L.S.).
Rula A Hajj-AliFrom the Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH (D.P.R.); Laboratory of Vascular Pathobiology, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI (D.P.R., Y.C., R.L.S.); Department of Rheumatologic and Immunologic Disease, Orthopedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, OH (R.A.H.-A.); and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI (R.L.S.).
Yiliang ChenFrom the Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH (D.P.R.); Laboratory of Vascular Pathobiology, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI (D.P.R., Y.C., R.L.S.); Department of Rheumatologic and Immunologic Disease, Orthopedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, OH (R.A.H.-A.); and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI (R.L.S.).
Roy L SilversteinFrom the Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, OH (D.P.R.); Laboratory of Vascular Pathobiology, Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI (D.P.R., Y.C., R.L.S.); Department of Rheumatologic and Immunologic Disease, Orthopedic and Rheumatologic Institute, Cleveland Clinic Foundation, Cleveland, OH (R.A.H.-A.); and Department of Medicine, Medical College of Wisconsin, Milwaukee, WI (R.L.S.). rsilverstein@mcw.edu.
Case Western Reserve University · USCleveland Clinic · USCleveland Clinic Lerner College of Medicine · US

Funding

Vascular signaling via scavenger receptorsP01HL046403 · NHLBI · WEILL MEDICAL COLL OF CORNELL UNIV · PI HAJJAR, KATHERINE AMBERSON · 1991 to 2011
$26.7M
REGULATION OF MONOCYTE 15-LIPOXYGENASE EXPRESSIONP01HL087018 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI MCINTYRE, THOMAS M · 2007 to 2011
$11.4M
Regulation of the anti-antiangiogenic switch by CD36, Thrombospondin, and HRGPR01HL085718 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SILVERSTEIN, ROY L · 2008 to 2012
$2.0M
Mechanistic Role of CD36 in ThrombosisR01HL111614 · NHLBI · MEDICAL COLLEGE OF WISCONSIN · PI SILVERSTEIN, ROY L · 2013 to 2017
$1.7M
NHLBI NIH HHS HL085718NHLBI NIH HHS P01 HL046403NHLBI NIH HHS P01 HL087018NHLBI NIH HHS R01 HL085718NHLBI NIH HHS R01 HL111614
6 · The paper itself

Abstract

objectiveLiterature on the effect of cell-derived extracellular vesicles (EV), ≤1 μm vesicles shed from various cell types during activation or apoptosis, on microvascular endothelial cell (MVEC) signaling is conflicting. Thrombospondin-1 and related proteins induce anti-angiogenic signals in MVEC via CD36. CD36 binds EV via phosphatidylserine exposed on their surface but the effects of this interaction on MVEC functions are not known. We hypothesized that EV would inhibit angiogenic MVEC functions via CD36. APPROACH AND

resultsEV generated in vitro from various cell types or isolated from plasma inhibited MVEC tube formation in in vitro matrigel assays and endothelial cell migration in Boyden chamber assays. Exosomes derived from the same cells did not have inhibitory activity. Inhibition of migration required endothelial cell expression of CD36. In mouse in vivo matrigel plug assays, EV inhibited cell migration into matrigel plugs in wild type but not in cd36 null animals. Annexin V, an anionic phospholipid binding protein, when incubated with EV partially reversed inhibition of migration, suggesting a phosphatidylserine-dependent effect. EV exposure induced reactive oxygen species generation in MVEC in a NADPH oxidase and Src family kinase-dependent manner, and their inhibition by apocynin and PP2, respectively, partially reversed the EV-mediated inhibition of migration. Annexin V partially reversed EV-induced reactive oxygen species generation in murine CD36 cDNA-transfected HVUEC but not in CD36-negative human umbilical vein endothelial cell.

conclusionsThese studies establish a general inhibitory effect of EV on endothelial cell proangiogenic responses and identify a CD36-mediated mechanistic pathway through which EV inhibit MVEC migration and tube formation.

Indexed as

Cell MovementNeovascularization, PhysiologicSignal TransductionAnimalsAnnexin A5CD36 AntigensCell Line, TumorEndothelial CellsEnzyme InhibitorsExtracellular VesiclesHumansHuman Umbilical Vein Endothelial CellsMaleMice, Inbred C57BLMice, KnockoutMicrovesselsAnnexin A5CD36 AntigensEnzyme InhibitorsNADPH OxidasesPhosphatidylserinesReactive Oxygen Speciessrc-Family KinasesangiogenesisCD36endothelial cellextracellular vesicles

Identifiers

PMID26821945
PMCPMC4767682
OpenAlexW2255848324

What OpenQuestion holds

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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.