Evidence map›Paper›PMID 26254821›Full record

ArticleJournal of vascular surgery2016

Subacute limb ischemia induces skeletal muscle injury in genetically susceptible mice independent of vascular density.

Joseph M McClung, Timothy J McCord, Kevin Southerland, Cameron A Schmidt, Michael E Padgett, Terence E Ryan, Christopher D Kontos

Open access · greenAbstract readComparative Study
In one paragraph

Article in Journal of vascular surgery, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
1.1field-weighted citation impact, top 24% 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

36 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
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  4. Murine hindlimb ischemia models: a narrative review.Frontiers in cardiovascular medicine · 2025
    Review
  5. Vascular adhesion molecule 1JVS-vascular science · 2025
    Article
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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

7 authors at 2 institutions in 1 country.

Joseph M McClungDepartment of Physiology, East Carolina University, Brody Medical Center, Greenville, NC; Diabetes and Obesity Institute, East Carolina Heart Institute, Brody Medical Center, Greenville, NC. Electronic address: mcclungj@ecu.edu.
Timothy J McCordDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
Kevin SoutherlandDivision of General Surgery, Department of Surgery, Duke University Medical Center, Durham, NC.
Cameron A SchmidtDepartment of Physiology, East Carolina University, Brody Medical Center, Greenville, NC; Diabetes and Obesity Institute, East Carolina Heart Institute, Brody Medical Center, Greenville, NC.
Michael E PadgettDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
Terence E RyanDepartment of Physiology, East Carolina University, Brody Medical Center, Greenville, NC; Diabetes and Obesity Institute, East Carolina Heart Institute, Brody Medical Center, Greenville, NC.
Christopher D KontosDivision of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC.
Duke Medical Center · USEast Carolina University · US

Funding

Genetic Determinants of Limb Pathology in Peripheral Artery DiseaseR01HL125695 · NHLBI · EAST CAROLINA UNIVERSITY · PI MCCLUNG, JOSEPH MATTHEW · 2015 to 2019
$1.9M
Skeletal Muscle and Vascular Remodeling in Peripheral Artery DiseaseR01HL124444 · NHLBI · DUKE UNIVERSITY · PI KONTOS, CHRISTOPHER D · 2015 to 2017
$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
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 HL124444NHLBI NIH HHS R01 HL125695NHLBI NIH HHS R21 HL118661NHLBI NIH HHS R56 HL124444
6 · The paper itself

Abstract

objectiveThe primary preclinical model of peripheral artery disease, which involves acute limb ischemia (ALI), can result in appreciable muscle injury that is attributed to the acuity of the ischemic injury. A less acute model of murine limb ischemia using ameroid constrictors (ACs) has been developed in an attempt to mimic the chronic nature of human disease. However, there is currently little understanding of how genetics influence muscle injury following subacute arterial occlusion in the mouse.

methodsWe investigated the influence of mouse genetics on skeletal muscle tissue survival, blood flow, and vascular density by subjecting two different mouse strains, C57BL/6 (BL6) and BALB/c, to ALI or subacute limb ischemia using single (1AC) or double (2AC) AC placement on the femoral artery.

resultsSimilar to ALI, the 2AC model resulted in significant tissue necrosis and limb perfusion deficits in genetically susceptible BALB/c but not BL6 mice. In the 1AC model, no outward evidence of tissue necrosis was observed, and there were no differences in limb blood flow between BL6 and BALB/c. However, BALB/c mice displayed significantly greater muscle injury, as evidenced by increased inflammation and myofiber atrophy, despite having no differences in CD31(+) and SMA(+) vascular density and area. BALB/c mice also displayed significantly greater centralized myonuclei, indicating increased muscle regeneration.

conclusionsThe susceptibility of skeletal muscle to ischemia-induced injury is at least partly independent of muscle blood flow and vascular density, consistent with a muscle cell autonomous response that is genetically determined. Further development of preclinical models of peripheral artery disease that more accurately reflect the nature of the human disease may allow more accurate identification of genetic targets for therapeutic intervention.

Indexed as

Neovascularization, PhysiologicActinsAnimalsBiomarkersBlood Flow VelocityDisease Models, AnimalFemoral ArteryGenetic Predisposition to DiseaseHindlimbIschemiaLigationMice, Inbred BALB CMice, Inbred C57BLMuscle DevelopmentMuscle, SkeletalNecrosisActa2 protein, mouseActinsBiomarkersPlatelet Endothelial Cell Adhesion Molecule-1

Identifiers

PMID26254821
PMCPMC4744137
OpenAlexW1078052544

What OpenQuestion holds

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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.