Evidence map›Paper›PMID 30482476›Full record

ArticleMolecular metabolism2019

Metformin intervention prevents cardiac dysfunction in a murine model of adult congenital heart disease.

Julia C Wilmanns, Raghav Pandey, Olivia Hon, Anjana Chandran, Jan M Schilling, Elvira Forte, Qizhu Wu, Gael Cagnone, Preeti Bais, Vivek Philip and 10 more

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

Article in Molecular metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.4field-weighted citation impact, top 39% 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

7 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Application of 4-D ultrasound-derived regional strain and proteomics analysis inAmerican journal of physiology. Heart and circulatory physiology · 2023
    Article
  6. Observational
  7. Review
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

20 authors at 8 institutions in 6 countries.

Julia C WilmannsAustralian Regenerative Medicine Institute, Monash University, Australia; Department of Cardiology and Angiology, Experimental Cardiology, Hannover Medical School, Germany.
Raghav PandeyThe Jackson Laboratory, USA.
Olivia HonThe Jackson Laboratory, USA.
Anjana ChandranAustralian Regenerative Medicine Institute, Monash University, Australia.
Jan M SchillingVA San Diego Healthcare System and Department of Anesthesiology, University of California San Diego, USA.
Elvira ForteThe Jackson Laboratory, USA.
Qizhu WuMonash Biomedical Imaging, Monash University, Australia.
Gael CagnoneDepartment of Pharmacology, Research Center of CHU Sainte-Justine, Canada.
Preeti BaisThe Jackson Laboratory, USA.
Vivek PhilipThe Jackson Laboratory, USA.
David ColemanThe Jackson Laboratory, USA.
Heidi KocalisThe Jackson Laboratory, USA.
Stuart K ArcherMonash Bioinformatics Platform, Monash University, Australia; Biomedicine Discovery Institute, Faculty of Medicine, Nursing and Health Sciences, Monash University, Australia.
James T PearsonMonash Biomedical Imaging, Monash University, Australia; Department of Physiology, Monash University, Australia; National Cerebral & Cardiovascular Center, Suita 565-8565, Japan.
Mirana RamialisonAustralian Regenerative Medicine Institute, Monash University, Australia; Systems Biology Institute, Australia.
Joerg HeinekeDepartment of Cardiology and Angiology, Experimental Cardiology, Hannover Medical School, Germany.
Hemal H PatelVA San Diego Healthcare System and Department of Anesthesiology, University of California San Diego, USA.
Nadia A RosenthalThe Jackson Laboratory, USA; Australian Regenerative Medicine Institute, Monash University, Australia; National Heart and Lung Institute, Imperial College London, W12 0NN, UK.
Milena B FurtadoThe Jackson Laboratory, USA; Australian Regenerative Medicine Institute, Monash University, Australia.
Mauro W CostaThe Jackson Laboratory, USA; Australian Regenerative Medicine Institute, Monash University, Australia. Electronic address: mauro.costa@jax.org.
Jackson Laboratory · USAustralian Regenerative Medicine Institute · AUUniversity of California San Diego · USCentre Hospitalier Universitaire Sainte-Justine · CADiscovery Institute · USMedizinische Hochschule Hannover · DEMonash University · AUNational Cerebral and Cardiovascular Center · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveCongenital heart disease (CHD) is the most frequent birth defect worldwide. The number of adult patients with CHD, now referred to as ACHD, is increasing with improved surgical and treatment interventions. However the mechanisms whereby ACHD predisposes patients to heart dysfunction are still unclear. ACHD is strongly associated with metabolic syndrome, but how ACHD interacts with poor modern lifestyle choices and other comorbidities, such as hypertension, obesity, and diabetes, is mostly unknown.

methodsWe used a newly characterized mouse genetic model of ACHD to investigate the consequences and the mechanisms associated with combined obesity and ACHD predisposition. Metformin intervention was used to further evaluate potential therapeutic amelioration of cardiac dysfunction in this model.

resultsACHD mice placed under metabolic stress (high fat diet) displayed decreased left ventricular ejection fraction. Comprehensive physiological, biochemical, and molecular analysis showed that ACHD hearts exhibited early changes in energy metabolism with increased glucose dependence as main cardiac energy source. These changes preceded cardiac dysfunction mediated by exposure to high fat diet and were associated with increased disease severity. Restoration of metabolic balance by metformin administration prevented the development of heart dysfunction in ACHD predisposed mice.

conclusionsThis study reveals that early metabolic impairment reinforces heart dysfunction in ACHD predisposed individuals and diet or pharmacological interventions can be used to modulate heart function and attenuate heart failure. Our study suggests that interactions between genetic and metabolic disturbances ultimately lead to the clinical presentation of heart failure in patients with ACHD. Early manipulation of energy metabolism may be an important avenue for intervention in ACHD patients to prevent or delay onset of heart failure and secondary comorbidities. These interactions raise the prospect for a translational reassessment of ACHD presentation in the clinic.

Indexed as

AnimalsCardiac OutputEnergy MetabolismHeart Defects, CongenitalHypoglycemic AgentsMaleMetabolic SyndromeMetforminMiceMice, Inbred C57BLVentricular Dysfunction, LeftHypoglycemic AgentsMetforminAdult congenital heart diseaseMetabolismMetforminObesity

Identifiers

PMID30482476
PMCPMC6358551
OpenAlexW2888035902

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY-NC-ND
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.