Evidence mapPaperPMID 31746130Full record

ArticleJournal of cellular and molecular medicine2020

VEGF signalling enhances lesion burden in KRIT1 deficient mice.

Peter V DiStefano, Angela J Glading

Open access · goldAbstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
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  7. Review
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  9. Article
  10. Review
  11. Article
  12. Review
  13. KRIT1 in vascular biology and beyond.Bioscience reports · 2024
    Review
  14. Article
  15. Article
  16. Review
  17. Article
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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

2 authors at 1 institution in 1 country.

Peter V DiStefanoDepartment of Pharmacology and Physiology, University of Rochester, Rochester, New York.
Angela J GladingDepartment of Pharmacology and Physiology, University of Rochester, Rochester, New York.ORCID 0000-0002-1830-6601
University of Rochester · US

Funding

Conformation-dependent regulation of KRIT1 and the CCM complexR01HL141131 · NHLBI · UNIVERSITY OF ROCHESTER · PI Angela J Glading · 2022 to 2022
$385k
NHLBI NIH HHS R01 HL117885NHLBI NIH HHS R01 HL141131NICHD NIH HHS R21 HD098576
6 · The paper itself

Abstract

The exact molecular mechanisms underlying CCM pathogenesis remain a complicated and controversial topic. Our previous work illustrated an important VEGF signalling loop in KRIT1 depleted endothelial cells. As VEGF is a major mediator of many vascular pathologies, we asked whether the increased VEGF signalling downstream of KRIT1 depletion was involved in CCM formation. Using an inducible KRIT1 endothelial-specific knockout mouse that models CCM, we show that VEGFR2 activation plays a role in CCM pathogenesis in mice. Inhibition of VEGFR2 using a specific inhibitor, SU5416, significantly decreased the number of lesions formed and slightly lowered the average lesion size. Notably, VEGFR2 inhibition also decreased the appearance of lesion haemorrhage as denoted by the presence of free iron in adjacent tissues. The presence of free iron correlated with increased microvessel permeability in both skeletal muscle and brain, which was completely reversed by SU5416 treatment. Finally, we show that VEGFR2 activation is a common downstream consequence of KRIT1, CCM2 and CCM3 loss of function, though the mechanism by which VEGFR2 activation occurs likely varies. Thus, our study clearly shows that VEGFR2 activation downstream of KRIT1 depletion enhances the severity of CCM formation in mice, and suggests that targeting VEGF signalling may be a potential future therapy for CCM.

Indexed as

AnimalsCells, CulturedEndothelial CellsHemangioma, Cavernous, Central Nervous SystemHemorrhagic StrokeKRIT1 ProteinMaleMiceMice, KnockoutPulmonary ArteryVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2KRIT1 ProteinKrit1 protein, mouseVascular Endothelial Growth Factor Avascular endothelial growth factor A, mouseVascular Endothelial Growth Factor Receptor-2angiogenesiscerebral cavernous malformationhaemorrhagic strokevascular endothelial growth factor

Identifiers

PMID31746130
PMCPMC6933401
OpenAlexW2990276791

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.