Evidence map›Paper›PMID 24523418›Full record

ArticleCirculation. Heart failure2014

Extracellular superoxide dismutase ameliorates skeletal muscle abnormalities, cachexia, and exercise intolerance in mice with congestive heart failure.

Mitsuharu Okutsu, Jarrod A Call, Vitor A Lira, Mei Zhang, Jean A Donet, Brent A French, Kyle S Martin, Shayn M Peirce-Cottler, Christopher M Rembold, Brian H Annex and 1 more

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

Article in Circulation. Heart failure, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
21.9field-weighted citation impact, top 1% 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

37 citing papers in PubMed, 75 citations in OpenAlex.

  1. Nutritional Risk Index predicts mortality in hospitalized advanced heart failure patients.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2015
    Trial
  2. Review
  3. Flow Cytometric Methods for ROS Quantification in Skeletal Muscle Myotubes.Methods in molecular biology (Clifton, N.J.) · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
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  11. Muscle p62 stimulates the expression of antioxidant proteins alleviating cancer cachexia.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023
    Article
  12. Article
  13. Gut microbiota in sarcopenia and heart failure.The journal of cardiovascular aging · 2022
    Article
  14. Review
  15. Exercise improves angiogenic function of circulating exosomes in type 2 diabetes: Role of exosomal SOD3.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  16. Article
  17. Review
  18. 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

11 authors at 1 institution in 1 country.

Mitsuharu OkutsuFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Jarrod A CallFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Vitor A LiraFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Mei ZhangFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Jean A DonetFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Brent A FrenchFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Kyle S MartinFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Shayn M Peirce-CottlerFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Christopher M RemboldFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Brian H AnnexFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.).
Zhen YanFrom the Departments of Medicine (M.O., J.A.C., V.A.L., M.Z., J.A.D., C.M.R., B.H.A., Z.Y.), Pharmacology (Z.Y.), and Molecular Physiology and Biological Physics (Z.Y.), Center for Skeletal Muscle Research (M.O., J.A.C., V.A.L., M.Z., J.A.D., Z.Y.), Robert M. Berne Cardiovascular Research Center, University of Virginia School of Medicine, Charlottesville, VA; and Department of Biomedical Engineering, University of Virginia, Charlottesville, VA (B.A.F., K.S.M., S.M.P.-C.). zhen.yan@virginia.edu.
Anna Needs Neuroblastoma Answers · US

Funding

BASIC CARDIOVASCULAR RESEARCH TRAINING GRANTT32HL007284 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI Brant E Isakson, Gary K Owens · 1985 to 2026
$19.6M
Arteriole/Venule Polarity in Adult MicrovasculatureR01HL082838 · NHLBI · UNIVERSITY OF VIRGINIA · PI PEIRCE-COTTLER, SHAYN · 2007 to 2011
$1.9M
NO-dependent SOD3 protection against cachexiaR21AR060444 · NIAMS · UNIVERSITY OF VIRGINIA · PI YAN, ZHEN · 2011 to 2012
$381k
NHLBI NIH HHS HL082838NHLBI NIH HHS R01 HL082838NHLBI NIH HHS T32 HL007284NHLBI NIH HHS T32-HL007284NIAMS NIH HHS AR060444NIAMS NIH HHS R21 AR060444
6 · The paper itself

Abstract

backgroundCongestive heart failure (CHF) is a leading cause of morbidity and mortality, and oxidative stress has been implicated in the pathogenesis of cachexia (muscle wasting) and the hallmark symptom, exercise intolerance. We have previously shown that a nitric oxide-dependent antioxidant defense renders oxidative skeletal muscle resistant to catabolic wasting. Here, we aimed to identify and determine the functional role of nitric oxide-inducible antioxidant enzyme(s) in protection against cardiac cachexia and exercise intolerance in CHF. METHODS AND

resultsWe demonstrated that systemic administration of endogenous nitric oxide donor S-nitrosoglutathione in mice blocked the reduction of extracellular superoxide dismutase (EcSOD) protein expression, as well as the induction of MAFbx/Atrogin-1 mRNA expression and muscle atrophy induced by glucocorticoid. We further showed that endogenous EcSOD, expressed primarily by type IId/x and IIa myofibers and enriched at endothelial cells, is induced by exercise training. Muscle-specific overexpression of EcSOD by somatic gene transfer or transgenesis (muscle creatine kinase [MCK]-EcSOD) in mice significantly attenuated muscle atrophy. Importantly, when crossbred into a mouse genetic model of CHF (α-myosin heavy chain-calsequestrin), MCK-EcSOD transgenic mice had significant attenuation of cachexia with preserved whole body muscle strength and endurance capacity in the absence of reduced HF. Enhanced EcSOD expression significantly ameliorated CHF-induced oxidative stress, MAFbx/Atrogin-1 mRNA expression, loss of mitochondria, and vascular rarefaction in skeletal muscle.

conclusionsEcSOD plays an important antioxidant defense function in skeletal muscle against cardiac cachexia and exercise intolerance in CHF.

Indexed as

AnimalsAntioxidantsCachexiaCreatine Kinase, MM FormDisease Models, AnimalExercise ToleranceHeart FailureMaleMiceMice, Inbred C57BLMice, TransgenicMuscle ProteinsMuscle, SkeletalPhysical Conditioning, AnimalRNA, MessengerSKP Cullin F-Box Protein LigasesAntioxidantsCreatine Kinase, MM FormFbxo32 protein, mouseMuscle ProteinsRNA, MessengerSKP Cullin F-Box Protein LigasesS-NitrosoglutathioneSuperoxide Dismutasecapillariesexercisemitochondriamuscular atrophyoxidative stress

Identifiers

PMID24523418
PMCPMC4080303
OpenAlexW2139216839

What OpenQuestion holds

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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.