Evidence map›Paper›PMID 24622514›Full record

ArticleScience translational medicine2014

TGF-β signaling mediates endothelial-to-mesenchymal transition (EndMT) during vein graft remodeling.

Brian C Cooley, Jose Nevado, Jason Mellad, Dan Yang, Cynthia St Hilaire, Alejandra Negro, Fang Fang, Guibin Chen, Hong San, Avram D Walts and 12 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 271 papers.

0numbers the graph read from it
0cells of the map it votes in
271citing papers in PubMed
13.8field-weighted citation impact, top 1% 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

271 citing papers in PubMed, 385 citations in OpenAlex.

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 3 institutions in 1 country.

Brian C Cooley *Department of Orthopaedic Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, 53226, USA.
Jose Nevado *National Institutes of Health-University of the Philippines College of Medicine, Ermita, Manila.
Jason Mellad *William Harvey Research Institute, Barts and the London NHS Trust, London, EC1M 6BQ, UK.
Dan YangCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Cynthia St HilaireCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Alejandra NegroCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Fang FangCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Guibin ChenCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Hong SanCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Avram D WaltsCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Robin L SchwartzbeckCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Brandi TaylorCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Jan D LanzerCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Andrew WraggCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Abdalla ElaghaCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Leilani E BeltranCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Colin BerryCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Robert FeilInterfaculty Institute of Biochemistry, Universität Tübingen, 72074 Tübingen, Germany.
Renu VirmaniCVPath Institute, Inc., Gaithersburg, Maryland, 20878, USA.
Elena LadichCVPath Institute, Inc., Gaithersburg, Maryland, 20878, USA.
Jason C KovacicCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
Manfred BoehmCenter for Molecular Medicine, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, 20892, USA.
National Heart Lung and Blood Institute · USNational Institutes of Health · USMedical College of Wisconsin · US

Funding

NHLBI Animal Program DivisionZIGHL006020 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI CLARK, TANNIA · 2009 to 2025
$47.3M
Light Microscopy CoreZICHL006019 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI COMBS, CHRISTIAN · 2009 to 2025
$29.3M
Murine models of vascular remodelingZIAHL006078 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI BOEHM, MANFRED · 2010 to 2025
$11.4M
Cellular and molecular mechanisms of endothelial repair and atherosclerosisK08HL111330 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVACIC, JASON CIRIL · 2012 to 2016
$647k
Intramural NIH HHS ZIA HL006078NHLBI NIH HHS K08 HL111330NHLBI NIH HHS K08HL111330
6 · The paper itself

Abstract

Veins grafted into an arterial environment undergo a complex vascular remodeling process. Pathologic vascular remodeling often results in stenosed or occluded conduit grafts. Understanding this complex process is important for improving the outcome of patients with coronary and peripheral artery disease undergoing surgical revascularization. Using in vivo murine cell lineage-tracing models, we show that endothelial-derived cells contribute to neointimal formation through endothelial-to-mesenchymal transition (EndMT), which is dependent on early activation of the Smad2/3-Slug signaling pathway. Antagonism of transforming growth factor-β (TGF-β) signaling by TGF-β neutralizing antibody, short hairpin RNA-mediated Smad3 or Smad2 knockdown, Smad3 haploinsufficiency, or endothelial cell-specific Smad2 deletion resulted in decreased EndMT and less neointimal formation compared to controls. Histological examination of postmortem human vein graft tissue corroborated the changes observed in our mouse vein graft model, suggesting that EndMT is operative during human vein graft remodeling. These data establish that EndMT is an important mechanism underlying neointimal formation in interpositional vein grafts, and identifies the TGF-β-Smad2/3-Slug signaling pathway as a potential therapeutic target to prevent clinical vein graft stenosis.

Indexed as

Signal TransductionAnimalsAntibodies, NeutralizingCell LineageCell TransdifferentiationEndothelial CellsGene Knockdown TechniquesHumansMesodermMiceNeointimaSmad2 ProteinSmad3 ProteinSnail Family Transcription FactorsTranscription FactorsTransforming Growth Factor betaAntibodies, NeutralizingSmad2 ProteinSmad3 ProteinSNAI1 protein, humanSnai2 protein, mouseSnail Family Transcription FactorsTranscription FactorsTransforming Growth Factor beta

Identifiers

PMID24622514
PMCPMC4181409
OpenAlexW2068200901

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.