Evidence map›Paper›PMID 11549592›Full record

ArticleThe American journal of pathology2001

Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide.

B Bussolati, C Dunk, M Grohman, C D Kontos, J Mason, A Ahmed

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

Article in The American journal of pathology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
91citing papers in PubMed, 2 pooled it
7.5field-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

91 citing papers in PubMed, 2 syntheses or guidelines pooled it, 284 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
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  5. Article
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  12. Article
  13. VEGFR1 signaling in retinal angiogenesis and microinflammation.Progress in retinal and eye research · 2021
    Review
  14. Article
  15. Article
  16. Genetic Scores ofInternational journal of environmental research and public health · 2021
    Article
  17. Review
  18. Article
  19. Article
  20. αAmerican journal of physiology. Cell physiology · 2019
    Article

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

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

6 authors at 3 institutions in 2 countries.

B BussolatiDepartment of Reproductive and Vascular Biology, The Medical School, University of Birmingham, Edgbaston, Birmingham, United Kingdom.
C Dunk
M Grohman
C D Kontos
J Mason
A Ahmed
University of Birmingham · GBDuke Medical Center · USImperial College London · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

The known responses of vascular endothelial growth factor (VEGF) are mediated through VEGF receptor-2 (VEGFR-2/KDR) in endothelial cells. However, it is unknown whether VEGFR-1 (Flt-1) is an inert decoy or a signaling receptor for VEGF during physiological or pathological angiogenesis. Here we report that VEGF-stimulated nitric oxide (NO) release is inhibited by blockade of VEGFR-1 and that VEGFR-1 via NO negatively regulates of VEGFR-2-mediated proliferation and promotes formation of capillary networks in human umbilical vein endothelial cells (HUVECs). Inhibition of VEGFR-1 in a murine Matrigel angiogenesis assay induced large aneurysm-like structures. VEGF-induced capillary growth over 14 days was inhibited by anti-VEGFR-2-blocking antibody as determined by reduced tube length between capillary connections (P < 0.0001) in an in vitro angiogenesis assay. In contrast, loss of VEGFR-1 activity with a neutralizing anti-VEGFR-1 antibody resulted in an increase in the accumulation of endothelial cells (P < 0.0001) and a dramatic decrease in the number of capillary connections that were restored by the addition of NO donor. Porcine aortic endothelial (PAE) cells expressing human VEGFR-1 but not VEGFR-2 plated on growth factor-reduced Matrigel rearranged into tube-like structures that were prevented by anti-VEGFR-1 antibody or a cGMP inhibitor. VEGF stimulated NO release from VEGFR-1- but not VEGFR-2-transfected endothelial cells and placenta growth factor-1 stimulated NO release in HUVECs. Blockade of VEGFR-1 increased VEGF-mediated HUVEC proliferation that was inhibited by NO donors, and potentiated by NO synthase inhibitors. These data indicate that VEGFR-1 is a signaling receptor that promotes endothelial cell differentiation into vascular tubes, in part by limiting VEGFR-2-mediated endothelial cell proliferation via NO, which seems to be a molecular switch for endothelial cell differentiation.

Indexed as

Cell DivisionCells, CulturedEndothelial Growth FactorsEndothelium, VascularHumansLymphokinesNeovascularization, PhysiologicNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroso CompoundsPenicillamineProtein IsoformsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesEndothelial Growth FactorsLymphokinesN-glucopyranosyl-N2-acetyl-S-nitrosopenicillaminamideNitric OxideNitric Oxide DonorsNitric Oxide SynthaseNitric Oxide Synthase Type IIINitroso CompoundsNOS3 protein, humanPenicillamineProtein IsoformsProto-Oncogene ProteinsReceptor Protein-Tyrosine KinasesReceptors, Growth FactorReceptors, Vascular Endothelial Growth FactorVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factors

Identifiers

PMID11549592
PMCPMC1850457
OpenAlexW1999296939

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.