Evidence map›Paper›PMID 34849650›Full record

ArticleCardiovascular research2022

Endothelial ARHGEF26 is an angiogenic factor promoting VEGF signalling.

Qiuyu Martin Zhu, Bryan T MacDonald, Taiji Mizoguchi, Mark Chaffin, Alison Leed, Alessandro Arduini, Edyta Malolepsza, Kasper Lage, Virendar K Kaushik, Sekar Kathiresan and 1 more

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

Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.5field-weighted citation impact, top 42% 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

10 citing papers in PubMed, 11 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Qiuyu Martin ZhuCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.ORCID 0000-0003-2751-7985
Bryan T MacDonaldCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.ORCID 0000-0002-2090-2066
Taiji MizoguchiCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.
Mark ChaffinCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.
Alison LeedCenter for the Development of Therapeutics, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.ORCID 0000-0001-5972-1548
Alessandro ArduiniCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.
Edyta MalolepszaGenomics Platform, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Kasper LageDepartment of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Virendar K KaushikCenter for the Development of Therapeutics, The Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sekar KathiresanCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.ORCID 0000-0002-3711-7101
Patrick T EllinorCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, 75 Ames Street, Cambridge, MA 02142, USA.ORCID 0000-0002-2067-0533
Broad Institute · US

Funding

IDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL092577
6 · The paper itself

Abstract

aimsGenetic studies have implicated the ARHGEF26 locus in the risk of coronary artery disease (CAD). However, the causal pathways by which DNA variants at the ARHGEF26 locus confer risk for CAD are incompletely understood. We sought to elucidate the mechanism responsible for the enhanced risk of CAD associated with the ARHGEF26 locus. METHODS AND

resultsIn a conditional analysis of the ARHGEF26 locus, we show that the sentinel CAD-risk signal is significantly associated with various non-lipid vascular phenotypes. In human endothelial cell (EC), ARHGEF26 promotes the angiogenic capacity, and interacts with known angiogenic factors and pathways. Quantitative mass spectrometry showed that one CAD-risk coding variant, rs12493885 (p.Val29Leu), resulted in a gain-of-function ARHGEF26 that enhances proangiogenic signalling and displays enhanced interactions with several proteins partially related to the angiogenic pathway. ARHGEF26 is required for endothelial angiogenesis by promoting macropinocytosis of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) on cell membrane and is crucial to Vascular Endothelial Growth Factor (VEGF)-dependent murine vessel sprouting ex vivo. In vivo, global or tissue-specific deletion of ARHGEF26 in EC, but not in vascular smooth muscle cells, significantly reduced atherosclerosis in mice, with enhanced plaque stability.

conclusionsOur results demonstrate that ARHGEF26 is involved in angiogenesis signaling, and that DNA variants within ARHGEF26 that are associated with CAD risk could affect angiogenic processes by potentiating VEGF-dependent angiogenesis.

Indexed as

Guanine Nucleotide Exchange FactorsVascular Endothelial Growth Factor Receptor-2AnimalsHumansMiceNeovascularization, PathologicNeovascularization, PhysiologicSignal TransductionVascular Endothelial Growth Factor AARHGEF26 protein, humanGuanine Nucleotide Exchange FactorsKDR protein, humanVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2angiogenesisatherosclerosiscoronary artery diseaseendothelial cell

Identifiers

PMID34849650
PMCPMC9586566
OpenAlexW3216450681

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.