Evidence map›Paper›PMID 26572549›Full record

ArticleJournal of the American Heart Association2015

Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Promotes Angiogenesis and Ischemia-Induced Neovascularization Via NADPH Oxidase 4 (NOX4) and Nitric Oxide-Dependent Mechanisms.

Belinda Ann Di Bartolo, Siân Peta Cartland, Leonel Prado-Lourenco, Thomas Scott Griffith, Carmine Gentile, Jayant Ravindran, Nor Saadah Muhammad Azahri, Thuan Thai, Amanda Wing Shee Yeung, Shane Ross Thomas and 1 more

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

Article in Journal of the American Heart Association, 2015. 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
2.4field-weighted citation impact, top 11% 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, 60 citations in OpenAlex.

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  17. The wHole Story About Fenestrations in LSEC.Frontiers in physiology · 2021
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  19. Article
  20. TRAIL signals, extracellular matrix and vessel remodelling.Vascular biology (Bristol, England) · 2020
    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 4 institutions in 2 countries.

Belinda Ann Di BartoloThe Heart Research Institute, Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.) The University of Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.).
Siân Peta CartlandThe Heart Research Institute, Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.) Centre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.) The University of Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.).
Leonel Prado-LourencoCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.).
Thomas Scott GriffithDepartment of Urology, The University of Minnesota, Minneapolis, MN (T.S.G.).
Carmine GentileThe Heart Research Institute, Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.) The University of Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.).
Jayant RavindranCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.) School of Medical Sciences, University of New South Wales, Sydney, Australia (J.R., T.T., S.R.T.).
Nor Saadah Muhammad AzahriCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.).
Thuan ThaiCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.) School of Medical Sciences, University of New South Wales, Sydney, Australia (J.R., T.T., S.R.T.).
Amanda Wing Shee YeungCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.).
Shane Ross ThomasCentre for Vascular Research, University of New South Wales, Sydney, Australia (S.P.C., L.P.L., J.R., N.S.M.A., T.T., A.W.S.Y., S.R.T.) School of Medical Sciences, University of New South Wales, Sydney, Australia (J.R., T.T., S.R.T.).
Mary Meltem KavurmaThe Heart Research Institute, Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.) The University of Sydney, NSW, Australia (B.A.D.B., S.P.C., C.G., M.M.K.).
UNSW Sydney · AUThe Heart Research Institute · AUUniversity of Sydney · AUUniversity of Minnesota · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has the ability to inhibit angiogenesis by inducing endothelial cell death, as well as being able to promote pro-angiogenic activity in vitro. These seemingly opposite effects make its role in ischemic disease unclear. Using Trail(-/-) and wildtype mice, we sought to determine the role of TRAIL in angiogenesis and neovascularization following hindlimb ischemia. METHODS AND

resultsReduced vascularization assessed by real-time 3-dimensional Vevo ultrasound imaging and CD31 staining was evident in Trail(-/-) mice after ischemia, and associated with reduced capillary formation and increased apoptosis. Notably, adenoviral TRAIL administration significantly improved limb perfusion, capillary density, and vascular smooth-muscle cell content in both Trail(-/-) and wildtype mice. Fibroblast growth factor-2, a potent angiogenic factor, increased TRAIL expression in human microvascular endothelial cell-1, with fibroblast growth factor-2-mediated proliferation, migration, and tubule formation inhibited with TRAIL siRNA. Both fibroblast growth factor-2 and TRAIL significantly increased NADPH oxidase 4 (NOX4) expression. TRAIL-inducible angiogenic activity in vitro was inhibited with siRNAs targeting NOX4, and consistent with this, NOX4 mRNA was reduced in 3-day ischemic hindlimbs of Trail(-/-) mice. Furthermore, TRAIL-induced proliferation, migration, and tubule formation was blocked by scavenging H2O2, or by inhibiting nitric oxide synthase activity. Importantly, TRAIL-inducible endothelial nitric oxide synthase phosphorylation at Ser-1177 and intracellular human microvascular endothelial cell-1 cell nitric oxide levels were NOX4 dependent.

conclusionsThis is the first report demonstrating that TRAIL can promote angiogenesis following hindlimb ischemia in vivo. The angiogenic effect of TRAIL on human microvascular endothelial cell-1 cells is downstream of fibroblast growth factor-2, involving NOX4 and nitric oxide signaling. These data have significant therapeutic implications, such that TRAIL may improve the angiogenic response to ischemia and increase perfusion recovery in patients with cardiovascular disease and diabetes.

Indexed as

Neovascularization, PhysiologicAnimalsApoptosisBiomarkersCapillariesCell MovementCell ProliferationCells, CulturedDisease Models, AnimalFemaleGenotypeHindlimbHumansIschemiaMice, Inbred C57BLMice, KnockoutBiomarkersNADPH Oxidase 4NADPH OxidasesNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanNOX4 protein, humanNox4 protein, mousePlatelet Endothelial Cell Adhesion Molecule-1TNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanTnfsf10 protein, mouseangiogenesisendothelial cellgene expressionischemia

Identifiers

PMID26572549
PMCPMC4845240
OpenAlexW2177453198

What OpenQuestion holds

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LicenceCC BY-NC
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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.