Evidence map›Paper›PMID 24578378›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2014

Mitogen-activated protein kinase phosphatase-1 promotes neovascularization and angiogenic gene expression.

Joel D Boerckel, Unnikrishnan M Chandrasekharan, Matthew S Waitkus, Emily G Tillmaand, Rebecca Bartlett, Paul E Dicorleto

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

Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
0.6field-weighted citation impact, top 32% 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

9 citing papers in PubMed, 14 citations in OpenAlex.

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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

6 authors at 1 institution in 1 country.

Joel D BoerckelFrom the Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, OH (J.D.B., U.M.C., M.S.W., E.G.T., R.B., P.E.D.); and Department of Aerospace and Mechanical Engineering, University of Notre Dame, IN (J.D.B.).
Unnikrishnan M Chandrasekharan
Matthew S Waitkus
Emily G Tillmaand
Rebecca Bartlett
Paul E Dicorleto
University of Notre Dame · US

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0M
Vascular Cell function and AtherosclerosisP01HL029582 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI SMITH, JONATHAN D · 1985 to 2019
$32.0M
Positive Role of MKP-1 in Angiogenesis.F32HL118969 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BOERCKEL, JOEL D · 2013 to 2013
$36k
NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1TR000439NHLBI NIH HHS F32 HL118969NHLBI NIH HHS F32-HL118969-01NHLBI NIH HHS P01 HL029582NHLBI NIH HHS P01-HL29582
6 · The paper itself

Abstract

objectiveAngiogenesis is the formation of new blood vessels through endothelial cell sprouting. This process requires the mitogen-activated protein kinases, signaling molecules that are negatively regulated by the mitogen-activated protein kinase phosphatase-1 (MKP-1). The purpose of this study was to evaluate the role of MKP-1 in neovascularization in vivo and identify associated mechanisms in endothelial cells. APPROACH AND

resultsWe used murine hindlimb ischemia as a model system to evaluate the role of MKP-1 in angiogenic growth, remodeling, and arteriogenesis in vivo. Genomic deletion of MKP-1 blunted angiogenesis in the distal hindlimb and microvascular arteriogenesis in the proximal hindlimb. In vitro, endothelial MKP-1 depletion/deletion abrogated vascular endothelial growth factor-induced migration and tube formation, and reduced proliferation. These observations establish MKP-1 as a positive mediator of angiogenesis and contrast with the canonical function of MKP-1 as a mitogen-activated protein kinase phosphatase, implying an alternative mechanism for MKP-1-mediated angiogenesis. Cloning and sequencing of MKP-1-bound chromatin identified localization of MKP-1 to exonic DNA of the angiogenic chemokine fractalkine, and MKP-1 depletion reduced histone H3 serine 10 dephosphorylation on this DNA locus and blocked fractalkine expression. In vivo, MKP-1 deletion abrogated ischemia-induced fractalkine expression and macrophage and T-lymphocyte infiltration in distal hindlimbs, whereas fractalkine delivery to ischemic hindlimbs rescued the effect of MKP-1 deletion on neovascular hindlimb recovery.

conclusionsMKP-1 promoted angiogenic and arteriogenic neovascular growth, potentially through dephosphorylation of histone H3 serine 10 on coding-region DNA to control transcription of angiogenic genes, such as fractalkine. These observations reveal a novel function for MKP-1 and identify MKP-1 as a potential therapeutic target.

Indexed as

Neovascularization, PhysiologicAnimalsBinding SitesCell MovementCell ProliferationCells, CulturedChemokine CX3CL1Disease Models, AnimalDual Specificity Phosphatase 1Endothelial CellsExonsGene Expression RegulationHindlimbHistonesHumansHuman Umbilical Vein Endothelial CellsChemokine CX3CL1CX3CL1 protein, humanCx3cl1 protein, mouseDual Specificity Phosphatase 1DUSP1 protein, humanDusp1 protein, mouseHistonesSerineangiogenesis effectMKP-1 phosphatase

Identifiers

PMID24578378
PMCPMC4121075
OpenAlexW2100393793

What OpenQuestion holds

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LicenceTDM
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.