Evidence map›Paper›PMID 34535195›Full record

ArticleBiology of sex differences2021

Spatiotemporal AMPKα2 deletion in mice induces cardiac dysfunction, fibrosis and cardiolipin remodeling associated with mitochondrial dysfunction in males only.

Lucile Grimbert, Maria-Nieves Sanz, Mélanie Gressette, Catherine Rucker-Martin, Marta Novotova, Audrey Solgadi, Ahmed Karoui, Susana Gomez, Kaveen Bedouet, Eric Jacquet and 6 more

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

10 citing papers in PubMed, 19 citations in OpenAlex.

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  5. Cardiomyopathies and a brief insight into DOX-induced cardiomyopathy.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2025
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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

16 authors at 3 institutions in 2 countries.

Lucile GrimbertFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Maria-Nieves SanzFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Mélanie GressetteFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Catherine Rucker-MartinUniversité Paris-Saclay, Inserm, Hypertension Artérielle Pulmonaire: Physiopathologie et Innovation Thérapeutique, 92350, Le Plessis Robinson, France.
Marta NovotovaDepartment of Cellular Cardiology, Institute of Experimental Endocrinology, Biomedical Research Center, University Science Park for Biomedicine, Slovak Academy of Sciences, Bratislava, Slovakia.
Audrey SolgadiService d'Analyse des Médicaments et Métabolites, Université Paris-Saclay, Inserm, CNRS, Institut Paris Saclay d'Innovation Thérapeutique, 92296, Châtenay-Malabry, France.
Ahmed KarouiFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Susana GomezFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Kaveen BedouetFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Eric JacquetUniversité Paris-Saclay, CNRS, Institut de Chimie Des Substances Naturelles, UPR 2301, 91198, Gif-sur-Yvette, France.
Christophe LemaireFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Vladimir VekslerFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Mathias MericskayFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Renée Ventura-ClapierFaculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Jérôme Piquereau *Faculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France. jerome.piquereau@universite-paris-saclay.fr.ORCID 0000-0002-6019-8683
Anne Garnier *Faculté de Pharmacie, UMR-S1180, INSERM, Université Paris-Saclay, 5 rue J-B Clément, 92296, Châtenay-Malabry, France.
Inserm · FRCentre National de la Recherche Scientifique · FRSlovak Academy of Sciences · SK

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe AMP-activated protein kinase (AMPK) is a major regulator of cellular energetics which plays key role in acute metabolic response and in long-term adaptation to stress. Recent works have also suggested non-metabolic effects.

methodsTo decipher AMPK roles in the heart, we generated a cardio-specific inducible model of gene deletion of the main cardiac catalytic subunit of AMPK (Ampkα2) in mice. This allowed us to avoid the eventual impact of AMPK-KO in peripheral organs.

resultsCardio-specific Ampkα2 deficiency led to a progressive left ventricular systolic dysfunction and the development of cardiac fibrosis in males. We observed a reduction in complex I-driven respiration without change in mitochondrial mass or in vitro complex I activity, associated with a rearrangement of the cardiolipins and reduced integration of complex I into the electron transport chain supercomplexes. Strikingly, none of these defects were present in females. Interestingly, suppression of estradiol signaling by ovariectomy partially mimicked the male sensitivity to AMPK loss, notably the cardiac fibrosis and the rearrangement of cardiolipins, but not the cardiac function that remained protected.

conclusionOur results confirm the close link between AMPK and cardiac mitochondrial function, but also highlight links with cardiac fibrosis. Importantly, we show that AMPK is differently involved in these processes in males and females, which may have clinical implications for the use of AMPK activators in the treatment of heart failure.

Indexed as

CardiolipinsHeart DiseasesAnimalsFemaleFibrosisMaleMiceMice, KnockoutMitochondriaCardiolipinsAMP-activated protein kinaseCardiolipinsEnergy metabolismFibrosisHeart

Identifiers

PMID34535195
PMCPMC8447586
OpenAlexW3199097123

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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.