Evidence map›Paper›PMID 27142980›Full record

ArticleCardiovascular research2016

Flt-1 (VEGFR-1) coordinates discrete stages of blood vessel formation.

John C Chappell, Julia G Cluceru, Jessica E Nesmith, Kevin P Mouillesseaux, Vanessa B Bradley, Caitlin M Hartland, Yasmin L Hashambhoy-Ramsay, Joseph Walpole, Shayn M Peirce, Feilim Mac Gabhann and 1 more

Open access · bronzeAbstract readVideo-Audio Media
In one paragraph

Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

33 citing papers in PubMed, 50 citations in OpenAlex.

  1. Review
  2. Endothelial Surface Glycocalyx in Vascular Functions and Diseases.Advances in experimental medicine and biology · 2026
    Review
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  9. Review
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  13. Cerebrovascular development: mechanisms and experimental approaches.Cellular and molecular life sciences : CMLS · 2021
    Review
  14. Pericyte migration and proliferation are tightly synchronized to endothelial cell sprouting dynamics.Integrative biology : quantitative biosciences from nano to macro · 2021
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. The pericyte microenvironment during vascular development.Microcirculation (New York, N.Y. : 1994) · 2019
    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

11 authors at 5 institutions in 1 country.

John C ChappellDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Center for Heart and Regenerative Medicine Research, Virginia Tech Carilion Research Institute, Roanoke, VA 24014, USA.
Julia G CluceruDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Jessica E NesmithCurriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Kevin P MouillesseauxDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Vanessa B BradleyCenter for Heart and Regenerative Medicine Research, Virginia Tech Carilion Research Institute, Roanoke, VA 24014, USA.
Caitlin M HartlandCenter for Heart and Regenerative Medicine Research, Virginia Tech Carilion Research Institute, Roanoke, VA 24014, USA.
Yasmin L Hashambhoy-RamsayDepartment of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.
Joseph WalpoleDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Shayn M PeirceDepartment of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
Feilim Mac GabhannDepartment of Biomedical Engineering and Institute for Computational Medicine, Johns Hopkins University, Baltimore, MD 21218, USA.
Victoria L BautchDepartment of Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA McAllister Heart Institute, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA bautch@med.unc.edu.
University of North Carolina at Chapel Hill · USJohns Hopkins University · USUniversity of Virginia · USVirginia Tech · USCarilion Roanoke Memorial Hospital · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007267 · NIGMS · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GARCIA-BLANCO, MARIANO A. · 1985 to 2024
$13.4M
MOLECULAR CONTROL OF ANGIOGENESISR01HL043174 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BAUTCH, VICTORIA L · 1989 to 2017
$4.7M
Endothelial cell decisions integrate soluble and matrix-bound VEGF gradientsR00HL093219 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MAC GABHANN, FEILIM C · 2009 to 2011
$746k
The Role of Vascular Flt-1 in Endothelial-Pericyte InteractionsK99HL105779 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHAPPELL, JOHN CHRISTOPHER · 2012 to 2013
$236k
Flt-1 (VEGFR-1) Regulation of Endothelial Cell Sprouting and Vessel MorphogenesisF32HL095359 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHAPPELL, JOHN CHRISTOPHER · 2009 to 2010
$102k
NHLBI NIH HHS F32 HL095359NHLBI NIH HHS K99 HL105779NHLBI NIH HHS R00 HL093219NHLBI NIH HHS R01 HL043174
6 · The paper itself

Abstract

aimsIn developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in the discrete stages of angiogenesis can uniquely contribute to vessel branching outcomes. METHODS AND

resultsTime-lapse movies of mammalian blood vessel development were used to define and quantify the dynamics of angiogenic sprouting. We characterized the formation of new functional conduits by classifying discrete sequential stages-sprout initiation, extension, connection, and stability-that are differentially affected by manipulation of vascular endothelial growth factor-A (VEGF-A) signalling via genetic loss of the receptor flt-1 (vegfr1). In mouse embryonic stem cell-derived vessels genetically lacking flt-1, overall branching is significantly decreased while sprout initiations are significantly increased. Flt-1(-/-) mutant sprouts are less likely to retract, and they form increased numbers of connections with other vessels. However, loss of flt-1 also leads to vessel collapse, which reduces the number of new stable conduits. Computational simulations predict that loss of flt-1 results in ectopic Flk-1 signalling in connecting sprouts post-fusion, causing protrusion of cell processes into avascular gaps and collapse of branches. Thus, defects in stabilization of new vessel connections offset increased sprout initiations and connectivity in flt-1(-/-) vascular networks, with an overall outcome of reduced numbers of new conduits.

conclusionsThese results show that VEGF-A signalling has stage-specific effects on vascular morphogenesis, and that understanding these effects on dynamic stages of angiogenesis and how they integrate to expand a vessel network may suggest new therapeutic strategies.

Indexed as

Neovascularization, PhysiologicAnimalsBlood VesselsCells, CulturedCell ShapeComputer SimulationEmbryonic Stem CellsEndothelial Progenitor CellsGene Expression Regulation, DevelopmentalMiceMicroscopy, VideoModels, CardiovascularMonte Carlo MethodMorphogenesisPhenotypeSignal TransductionFlt1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-1AngiogenesisComputational modelES cellsFlt-1VEGF-A

Identifiers

PMID27142980
PMCPMC4909163
OpenAlexW2346601542

What OpenQuestion holds

Textmetadata
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.