Evidence map›Paper›PMID 31430834›Full record

ArticleJournal of cachexia, sarcopenia and muscle2020

Divergent skeletal muscle mitochondrial phenotype between male and female patients with chronic heart failure.

Jack O Garnham, Lee D Roberts, Talia Caspi, Moza M Al-Owais, Max Bullock, Peter P Swoboda, Aaron Koshy, John Gierula, Maria F Paton, Richard M Cubbon and 3 more

Open access · goldAbstract read
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
4.1field-weighted citation impact, top 7% 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

17 citing papers in PubMed, 23 citations in OpenAlex.

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  11. Senescence in Post-Mitotic Cells: A Driver of Aging?Antioxidants & redox signaling · 2021
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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

13 authors at 1 institution in 1 country.

Jack O GarnhamLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Lee D RobertsLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Talia CaspiLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Moza M Al-OwaisLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Max BullockLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Peter P SwobodaLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Aaron KoshyLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
John GierulaLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Maria F PatonLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Richard M CubbonLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
Mark T KearneyLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
T Scott BowenSchool of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, UK.ORCID 0000-0002-1740-2474
Klaus K WitteLeeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK.
University of Leeds · GB

Funding

British Heart Foundation CH/13/1/30086British Heart Foundation FS/12/80/29821British Heart Foundation RG/15/7/31521Department of Health NIHR-CS-012-032Diabetes UK 16/0005382Medical Research Council MR/S025472/1
6 · The paper itself

Abstract

backgroundPrevious studies in heart failure with reduced ejection fraction (HFrEF) suggest that skeletal muscle mitochondrial impairments are associated with exercise intolerance in men. However, the nature of this relationship in female patients remains to be elucidated. This study aimed to determine the relationship between skeletal muscle mitochondrial impairments and exercise intolerance in male and female patients with HFrEF.

methodsMitochondrial respiration, enzyme activity, and gene expression were examined in pectoralis major biopsies from age-matched male (n = 45) and female (n = 11) patients with HFrEF and healthy-matched male (n = 24) and female (n = 11) controls. Mitochondrial variables were compared between sex and related to peak exercise capacity.

resultsCompared with sex-matched controls, complex I mitochondrial oxygen flux was 17% (P = 0.030) and 29% (P = 0.013) lower in male and female patients with HFrEF, respectively, which correlated to exercise capacity (r = 0.71; P > 0.0001). Female HFrEF patients had a 32% (P = 0.023) lower mitochondrial content compared with controls. However, after adjusting for mitochondrial content, male patients demonstrated lower complex I function by 15% (P = 0.030). Expression of key mitochondrial genes regulating organelle dynamics and maintenance (i.e. optic atrophy 1, peroxisome proliferator-activated receptor γ coactivator-1α, NADH:ubiquinone oxidoreductase core subunit S1/S3, and superoxide dismutase 2) were selectively lower in female HFrEF patients.

conclusionsThese data provide novel evidence that HFrEF induces divergent sex-specific mitochondrial phenotypes in skeletal muscle that predispose towards exercise intolerance, impacting mitochondrial 'quantity' in female patients and mitochondrial 'quality' in male patients. Therapeutic strategies to improve exercise tolerance in HFrEF should consider targeting sex-specific mitochondrial abnormalities in skeletal muscle.

Indexed as

AgedChronic DiseaseFemaleHeart FailureHumansMaleMitochondriaMuscle, SkeletalPhenotypeExercise intoleranceHFrEFMitochondrial dysfunctionOPA1Sex

Identifiers

PMID31430834
PMCPMC7015245
OpenAlexW2969316989

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.