Evidence map›Paper›PMID 28009297›Full record

ArticleCell reports2016

Integrative Analysis of PRKAG2 Cardiomyopathy iPS and Microtissue Models Identifies AMPK as a Regulator of Metabolism, Survival, and Fibrosis.

J Travis Hinson, Anant Chopra, Andre Lowe, Calvin C Sheng, Rajat M Gupta, Rajarajan Kuppusamy, John O'Sullivan, Glenn Rowe, Hiroko Wakimoto, Joshua Gorham and 8 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Cell reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
5.7field-weighted citation impact, top 3% 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

55 citing papers in PubMed, 94 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Observational
  5. Article
  6. Review
  7. Temporal dysregulation ofResearch square · 2025
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Cardiomyocyte infection byFrontiers in cellular and infection microbiology · 2023
    Article
  15. PRKAG2 Cardiomyopathy.Arquivos brasileiros de cardiologia · 2022
    Article
  16. Review
  17. Review
  18. Reading Frame Repair ofCirculation · 2022
    Article
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 8 institutions in 1 country.

J Travis HinsonThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA; Cardiology Center, University of Connecticut Health, Farmington, CT 06030, USA. Electronic address: travis.hinson@jax.org.
Anant ChopraDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Andre LoweThe Jackson Laboratory for Genomic Medicine, Farmington, CT 06032, USA.
Calvin C ShengDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Rajat M GuptaDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Rajarajan KuppusamyDivision of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
John O'SullivanDivision of Cardiovascular Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Glenn RoweDivision of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Hiroko WakimotoDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Joshua GorhamDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Michael A BurkeDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Kehan ZhangDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Kiran MusunuruPenn Cardiovascular Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
Robert E GersztenDivision of Cardiovascular Medicine, Massachusetts General Hospital, Boston, MA 02114, USA; Division of Cardiovascular Medicine, Beth Israel Deaconess Hospital, Boston, MA 02115, USA.
Sean M WuDivision of Cardiovascular Medicine, Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Christopher S ChenDepartment of Biomedical Engineering, Boston University, Boston, MA 02215, USA; The Wyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA 02115, USA.
Jonathan G SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Christine E SeidmanDepartment of Genetics, Harvard Medical School, Boston, MA 02115, USA; Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Electronic address: cseidman@genetics.med.harvard.edu.
Harvard University · USJackson Laboratory · USMassachusetts General Hospital · USStanford University · USBrigham and Women's Hospital · USHoward Hughes Medical Institute · USPenn Center for AIDS Research · USUniversity of Alabama at Birmingham · US

Funding

RESBIO - the Technology Resource for Polymeric BiomaterialsP41EB001046 · NIBIB · RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK · PI KOHN, JOACHIM B. · 2003 to 2017
$17.0M
Defining Pathways from Gene Mutation to Heart FailureR01HL080494 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI CHEN, CHRISTOPHER S, SEIDMAN, CHRISTINE E · 2005 to 2024
$9.4M
Induced pluripotent stem cells in the understanding and treatment of heart diseaseU01HL099776 · NHLBI · STANFORD UNIVERSITY · PI LONGAKER, MICHAEL T, WU, JOSEPH C. · 2009 to 2015
$8.2M
Tissue Chips for Rare Disease: Adding Timothy Syndrome to the HeLIVaSkCa platformUH3EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2014 to 2016
$7.1M
Molecular Signaling in Hypertrophic CardiomyopathyR01HL084553 · NHLBI · HARVARD MEDICAL SCHOOL · PI SEIDMAN, JONATHAN G · 2007 to 2022
$5.9M
Enabling Technologies for Human-Machine Hybrid TissuesDP1LM012179 · NLM · STANFORD UNIVERSITY · PI WU, SEAN M · 2014 to 2018
$3.8M
Generation of functional organs via developmental chimerismDP2OD004411 · OD · STANFORD UNIVERSITY · PI WU, SEAN M · 2008 to 2008
$2.5M
From association to function at the PHACTR1 GWAS locus for coronary atherosclerosisK08HL128810 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI GUPTA, RAJAT M · 2016 to 2020
$855k
Metabolic and developmental regulation by AMPK in PRKAG2-associated cardiomyopathyK08HL125807 · NHLBI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HINSON, JOHN TRAVIS · 2015 to 2019
$803k
Regulation of Mitochondria by Exercise and PGC-1 Coactivators in Skeletal MuscleK01AR062128 · NIAMS · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI ROWE, GLENN CAMERON · 2012 to 2016
$621k
Howard Hughes Medical InstituteNHLBI NIH HHS K08 HL125807NHLBI NIH HHS K08 HL128810NHLBI NIH HHS R01 HL080494NHLBI NIH HHS R01 HL084553NHLBI NIH HHS U01 HL099776NIAMS NIH HHS K01 AR062128NIBIB NIH HHS P41 EB001046NIBIB NIH HHS UH3 EB017103NIH HHS DP2 OD004411NLM NIH HHS DP1 LM012179
6 · The paper itself

Abstract

AMP-activated protein kinase (AMPK) is a metabolic enzyme that can be activated by nutrient stress or genetic mutations. Missense mutations in the regulatory subunit, PRKAG2, activate AMPK and cause left ventricular hypertrophy, glycogen accumulation, and ventricular pre-excitation. Using human iPS cell models combined with three-dimensional cardiac microtissues, we show that activating PRKAG2 mutations increase microtissue twitch force by enhancing myocyte survival. Integrating RNA sequencing with metabolomics, PRKAG2 mutations that activate AMPK remodeled global metabolism by regulating RNA transcripts to favor glycogen storage and oxidative metabolism instead of glycolysis. As in patients with PRKAG2 cardiomyopathy, iPS cell and mouse models are protected from cardiac fibrosis, and we define a crosstalk between AMPK and post-transcriptional regulation of TGFβ isoform signaling that has implications in fibrotic forms of cardiomyopathy. Our results establish critical connections among metabolic sensing, myocyte survival, and TGFβ signaling.

Indexed as

AMP-Activated Protein KinasesAnimalsCardiomyopathiesCell SurvivalGlycogenHumansHypertrophy, Left VentricularInduced Pluripotent Stem CellsMetabolomeMiceMuscle CellsMutation, MissenseSequence Analysis, RNASignal TransductionTissue EngineeringTransforming Growth Factor beta1AMP-Activated Protein KinasesGlycogenPRKAG2 protein, humanTransforming Growth Factor beta1AMP-activated protein kinaseAMPKfibrosisglycogen storage diseasehypertrophic cardiomyopathyPRKAG2TGF-betaWolff-Parkinson-White syndrome

Identifiers

PMID28009297
PMCPMC5193246
OpenAlexW2563313653

What Socratic holds

Textmetadata
LicenceTDM
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.