Evidence map›Paper›PMID 25956888›Full record

ArticleJournal of cell science2015

Autocrine VEGF maintains endothelial survival through regulation of metabolism and autophagy.

Courtney K Domigan, Carmen M Warren, Vaspour Antanesian, Katharina Happel, Safiyyah Ziyad, Sunyoung Lee, Abigail Krall, Lewei Duan, Antoni X Torres-Collado, Lawrence W Castellani and 5 more

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

Article in Journal of cell science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
6.1field-weighted citation impact, top 3% 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

99 citing papers in PubMed, 173 citations in OpenAlex.

  1. Article
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  16. EndothelialFrontiers in cell and developmental biology · 2025
    Article
  17. Review
  18. Article
  19. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024
    Article
  20. Autophagy as a Guardian of Vascular Niche Homeostasis.International journal of molecular sciences · 2024
    Review

39 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

15 authors at 2 institutions in 2 countries.

Courtney K DomiganDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Carmen M WarrenDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Vaspour AntanesianDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Katharina HappelAngiogenesis and Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Safiyyah ZiyadDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Sunyoung LeeDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Abigail KrallMolecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Lewei DuanDepartment of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Antoni X Torres-ColladoDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA.
Lawrence W CastellaniDepartment of Medicine, University of California, Los Angeles, CA 90024, USA.
David ElashoffDepartment of Medicine Statistics Core, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Heather R ChristofkMolecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Alexander M van der BliekJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90024, USA Biological Chemistry, University of California, Los Angeles, Los Angeles, CA 90024, USA.
Michael PotenteAngiogenesis and Metabolism Laboratory, Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
M Luisa Iruela-ArispeDepartment of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90024, USA Molecular Biology Institute, University of California, Los Angeles, CA 90024, USA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90024, USA arispe@mcdb.ucla.edu.
University of California, Los Angeles · USMax Planck Institute for Heart and Lung Research · DE

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
VEGF Signaling and Tumor MicroenvironmentR01CA126935 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI IRUELA-ARISPE, M. LUISA · 2007 to 2011
$1.4M
Contributions of mitochondrial fission proteins to mitophagyU01GM109764 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VAN DER BLIEK, ALEXANDER M · 2014 to 2017
$1.1M
NCATS NIH HHS UL1 TR000124NCI NIH HHS JCCC/P30CA016042NCI NIH HHS P30 CA016042NCI NIH HHS R01 CA126935NHLBI NIH HHS T32 HL069766NIDDK NIH HHS CURE/P30 DK041301NIDDK NIH HHS P30 DK041301NIGMS NIH HHS T32 GM007185NIGMS NIH HHS U01 GM109764
6 · The paper itself

Abstract

Autocrine VEGF is necessary for endothelial survival, although the cellular mechanisms supporting this function are unknown. Here, we show that--even after full differentiation and maturation--continuous expression of VEGF by endothelial cells is needed to sustain vascular integrity and cellular viability. Depletion of VEGF from the endothelium results in mitochondria fragmentation and suppression of glucose metabolism, leading to increased autophagy that contributes to cell death. Gene-expression profiling showed that endothelial VEGF contributes to the regulation of cell cycle and mitochondrial gene clusters, as well as several--but not all--targets of the transcription factor FOXO1. Indeed, VEGF-deficient endothelium in vitro and in vivo showed increased levels of FOXO1 protein in the nucleus and cytoplasm. Silencing of FOXO1 in VEGF-depleted cells reversed expression profiles of several of the gene clusters that were de-regulated in VEGF knockdown, and rescued both cell death and autophagy phenotypes. Our data suggest that endothelial VEGF maintains vascular homeostasis through regulation of FOXO1 levels, thereby ensuring physiological metabolism and endothelial cell survival.

Indexed as

ApoptosisAutocrine CommunicationAutophagyAnimalsBiomarkersBlotting, WesternCell DifferentiationCell ProliferationCells, CulturedEndothelium, VascularForkhead Box Protein O1Forkhead Transcription FactorsGene Expression ProfilingHumansHypoxiaMiceBiomarkersForkhead Box Protein O1Forkhead Transcription FactorsFOXO1 protein, humanRNA, MessengerVascular Endothelial Growth Factor AFOXO1Signal transductionVascular biology

Identifiers

PMID25956888
PMCPMC4487014
OpenAlexW2140642422

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.