Evidence map›Paper›PMID 26042050›Full record

ArticleFrontiers in physiology2015

Muscle cell derived angiopoietin-1 contributes to both myogenesis and angiogenesis in the ischemic environment.

Joseph M McClung, Jessica L Reinardy, Sarah B Mueller, Timothy J McCord, Christopher D Kontos, David A Brown, Sabah N A Hussain, Cameron A Schmidt, Terence E Ryan, Tom D Green

Open access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

25 citing papers in PubMed, 36 citations in OpenAlex.

  1. Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle.American journal of physiology. Regulatory, integrative and comparative physiology · 2016
    Trial
  2. Review
  3. Article
  4. Estrogen-Related Receptor Alpha Promotes Skeletal Muscle Regeneration and Mitigates Muscular Dystrophy.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
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  6. Review
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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

10 authors at 4 institutions in 2 countries.

Joseph M McClungDepartment of Physiology, Brody School of Medicine at East Carolina University Greenville, NC, USA ; Diabetes and Obesity Institute, Brody School of Medicine at East Carolina University Greenville, NC, USA.
Jessica L ReinardyDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine Durham, NC, USA.
Sarah B MuellerDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine Durham, NC, USA ; Medical Scientist Training Program, Duke University School of Medicine Durham, NC, USA.
Timothy J McCordDivision of Cardiology, Department of Medicine, Duke University Medical Center Durham, NC, USA.
Christopher D KontosDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine Durham, NC, USA ; Medical Scientist Training Program, Duke University School of Medicine Durham, NC, USA ; Division of Cardiology, Department of Medicine, Duke University Medical Center Durham, NC, USA.
David A BrownDepartment of Physiology, Brody School of Medicine at East Carolina University Greenville, NC, USA ; Diabetes and Obesity Institute, Brody School of Medicine at East Carolina University Greenville, NC, USA.
Sabah N A HussainMeakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Royal Victoria Hospital, McGill University Montreal, QC, Canada ; Department of Critical Care, McGill University Health Centre, Royal Victoria Hospital, McGill University Montreal, QC, Canada.
Cameron A SchmidtDepartment of Physiology, Brody School of Medicine at East Carolina University Greenville, NC, USA ; Diabetes and Obesity Institute, Brody School of Medicine at East Carolina University Greenville, NC, USA.
Terence E RyanDepartment of Physiology, Brody School of Medicine at East Carolina University Greenville, NC, USA ; Diabetes and Obesity Institute, Brody School of Medicine at East Carolina University Greenville, NC, USA.
Tom D GreenDepartment of Physiology, Brody School of Medicine at East Carolina University Greenville, NC, USA ; Diabetes and Obesity Institute, Brody School of Medicine at East Carolina University Greenville, NC, USA.
East Carolina University · USDuke University · USDuke Medical Center · USRoyal Victoria Regional Health Centre · CA

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007171 · NIGMS · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 1985 to 2021
$31.2M
Genetic Determinants of Limb Pathology in Peripheral Artery DiseaseR01HL125695 · NHLBI · EAST CAROLINA UNIVERSITY · PI MCCLUNG, JOSEPH MATTHEW · 2015 to 2019
$1.9M
Mitochondrial respirasomes in acute coronary syndromesR01HL123647 · NHLBI · VIRGINIA POLYTECHNIC INST AND ST UNIV · PI HULVER, MATTHEW W, SHAIKH, SAAME R · 2015 to 2018
$1.4M
Peripheral endothelial and muscle cell pathology in cardiovascular diseaseR00HL103797 · NHLBI · EAST CAROLINA UNIVERSITY · PI MCCLUNG, JOSEPH MATTHEW · 2014 to 2016
$744k
Skeletal Muscle and Vascular Remodeling in Peripheral Artery DiseaseR56HL124444 · NHLBI · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 2014 to 2014
$516k
Muscle-Resident Stem Cells for Angiogenesis and Vascular Maturation in PADR21HL118661 · NHLBI · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 2013 to 2014
$407k
Mitochondrial respirasomes in acute coronary syndromesR56HL123647 · NHLBI · EAST CAROLINA UNIVERSITY · PI BROWN, DAVID AVERY · 2014 to 2014
$295k
Peripheral endothelial and muscle cell pathology in cardiovascular diseaseK99HL103797 · NHLBI · DUKE UNIVERSITY · PI MCCLUNG, JOSEPH MATTHEW · 2010 to 2011
$246k
NHLBI NIH HHS K99 HL103797NHLBI NIH HHS R00 HL103797NHLBI NIH HHS R01 HL123647NHLBI NIH HHS R01 HL125695NHLBI NIH HHS R21 HL118661NHLBI NIH HHS R56 HL123647NHLBI NIH HHS R56 HL124444NIGMS NIH HHS T32 GM007171
6 · The paper itself

Abstract

Recent strategies to treat peripheral arterial disease (PAD) have focused on stem cell based therapies, which are believed to result in local secretion of vascular growth factors. Little is known, however, about the role of ischemic endogenous cells in this context. We hypothesized that ischemic muscle cells (MC) are capable of secreting growth factors that act as potent effectors of the local cellular regenerative environment. Both muscle and endothelial cells (ECs) were subjected to experimental ischemia, and conditioned medium (CM) from each was collected and analyzed to assess myogenic and/or angiogenic potential. In muscle progenitors, mRNA expression of VEGF and its cognate receptors (Nrp1, Flt, Flk) was present and decreased during myotube formation in vitro, and EC CM or VEGF increased myoblast proliferation. Angiopoietin-1 (Ang-1), Tie1, and Tie2 mRNA increased during MC differentiation in vitro. Exogenous Ang-1 enhanced myogenic (MyoD and Myogenin) mRNA in differentiating myoblasts and increased myosin heavy chain protein. Myotube formation was enhanced by MC CM and inhibited by EC CM. Ang-1 protein was present in CM from MCs isolated from both the genetically ischemia-susceptible BALB/c and ischemia-resistant C57BL/6 mouse strains, and chimeric Tie2 receptor trapping in situ ablated Ang-1's myogenic effects in vitro. Ang-1 or MC CM enhanced myotube formation in a mixed isolate of muscle progenitors as well as a myoblast co-culture with pluripotent mesenchymal cells (10T1/2) and this effect was abrogated by viral expression of the extracellular domain of Tie2 (AdsTie2). Furthermore, mesh/tube formation by HUVECs was enhanced by Ang-1 or MC CM and abrogated by Tie2 chimeric receptor trapping. Our results demonstrate the ability of muscle and endothelial cell-derived vascular growth factors, particularly Ang-1, to serve as multi-functional stimuli regulating crosstalk between blood vessels and muscle cells during regeneration from ischemic myopathy.

Indexed as

angiogenesisischemiamuscleparacrineprogenitor cellregenerationvascular disease

Identifiers

PMID26042050
PMCPMC4436568
OpenAlexW1921139382

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.