Evidence map›Paper›PMID 39312445›Full record

ArticleCardiovascular research2024

GDF15 antagonism limits severe heart failure and prevents cardiac cachexia.

Minoru Takaoka, John A Tadross, Ali B A K Al-Hadithi, Xiaohui Zhao, Rocío Villena-Gutiérrez, Jasper Tromp, Shazia Absar, Marcus Au, James Harrison, Anthony P Coll and 8 more

Abstract read
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In one paragraph

Article in Cardiovascular research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

28 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

18 authors.

Minoru TakaokaDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.ORCID 0000-0002-8515-8282
John A TadrossMetabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science and Medical Research Council, University of Cambridge, Cambridge, UK.ORCID 0000-0002-8424-1252
Ali B A K Al-HadithiDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.ORCID 0000-0003-0417-9653
Xiaohui ZhaoDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.
Rocío Villena-GutiérrezCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Jasper TrompUniversity of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.ORCID 0000-0001-6043-0713
Shazia AbsarDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.
Marcus AuDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.
James HarrisonDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.
Anthony P CollMetabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science and Medical Research Council, University of Cambridge, Cambridge, UK.ORCID 0000-0003-2594-7463
Stefan J MarciniakCambridge Institute for Medical Research, Cambridge Biomedical Campus, University of Cambridge, Cambridge, UK.ORCID 0000-0001-8472-7183
Debra RimmingtonMetabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science and Medical Research Council, University of Cambridge, Cambridge, UK.ORCID 0000-0002-3715-3970
Eduardo OliverCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Borja IbáñezCentro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.ORCID 0000-0002-5036-254X
Adriaan A VoorsUniversity of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
Stephen O'RahillyMetabolic Diseases Unit, Wellcome-MRC Institute of Metabolic Science and Medical Research Council, University of Cambridge, Cambridge, UK.
Ziad MallatDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.ORCID 0000-0003-0443-7878
Jane C GoodallDepartment of Medicine, Victor Phillip Dahdaleh Heart and Lung Research Institute, University of Cambridge, Cambridge CB2 0QQ, UK.ORCID 0000-0002-3761-161X

Funding

ALUKBritish Heart Foundation G101517Cambridge BHF Centre of Research Excellence 18/1/34212Cambridge Biomedical Research Centre BRC-1215-20014EPSRC EP/R03558X/1ERC Consolidator Grant 819775Inserm, FranceISCIII P-FIS fellowship FI17/00045MCIN/AEI Ramon y Cajal RYC2020-028884-IMedical Research Council MCMB MR/V028669/1Medical Research Council MR/R009120/1Medical Research Council MR/Y011813/1MRC MR/V028669/1MRC Metabolic Diseases Unit MC_UU_0014/1NIHR Cambridge Biomedical Research Centre NIHR203312Victor Philip Dahdaleh Foundation RG90505
6 · The paper itself

Abstract

aimsHeart failure and associated cachexia is an unresolved and important problem. This study aimed to determine the factors that contribute to cardiac cachexia in a new model of heart failure in mice that lack the integrated stress response (ISR) induced eIF2α phosphatase, PPP1R15A. METHODS AND

resultsMice were irradiated and reconstituted with bone marrow cells. Mice lacking functional PPP1R15A, exhibited dilated cardiomyopathy and severe weight loss following irradiation, whilst wild-type mice were unaffected. This was associated with increased expression of Gdf15 in the heart and increased levels of GDF15 in circulation. We provide evidence that the blockade of GDF15 activity prevents cachexia and slows the progression of heart failure. We also show the relevance of GDF15 to lean mass and protein intake in patients with heart failure.

conclusionOur data suggest that cardiac stress mediates a GDF15-dependent pathway that drives weight loss and worsens cardiac function. Blockade of GDF15 could constitute a novel therapeutic option to limit cardiac cachexia and improve clinical outcomes in patients with severe systolic heart failure.

Indexed as

CachexiaDisease Models, AnimalGrowth Differentiation Factor 15Heart FailureMice, Inbred C57BLMice, KnockoutAgedAnimalsBone Marrow TransplantationCardiomyopathy, DilatedFemaleHumansMaleMiceMiddle AgedMyocardiumGDF15 protein, humanGdf15 protein, mouseGrowth Differentiation Factor 15Protein Phosphatase 1CachexiaGDF15Heart failureIntegrated stress responsePPP1R15A

Identifiers

PMID39312445
PMCPMC11687397

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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.