Evidence map›Paper›PMID 34102853›Full record

ArticleCirculation2021

PKM1 Exerts Critical Roles in Cardiac Remodeling Under Pressure Overload in the Heart.

Qinfeng Li, Chao Li, Abdallah Elnwasany, Gaurav Sharma, Yu A An, Guangyu Zhang, Waleed M Elhelaly, Jun Lin, Yingchao Gong, Guihao Chen and 19 more

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

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
6.7field-weighted citation impact, top 2% 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

47 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Analysis of serum NMR metabolomics in fibrotic diseases of the myocardium.Metabolomics : Official journal of the Metabolomic Society · 2026
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  13. Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
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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

29 authors at 9 institutions in 2 countries.

Qinfeng LiDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (Q.L., J.Lin, Y.G., M.W., G.F.).
Chao LiDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Abdallah ElnwasanyDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Gaurav SharmaAdvanced Imaging Research Center (G.S., C.R.M.), University of Texas Southwestern Medical Center, Dallas.
Yu A AnTouchstone Diabetes Center, Department of Internal Medicine (Y.A.A., S.Z., Y.D., P.E.S.), University of Texas Southwestern Medical Center, Dallas.
Guangyu Zhang
Waleed M ElhelalyDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Jun LinDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (Q.L., J.Lin, Y.G., M.W., G.F.).
Yingchao GongDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (Q.L., J.Lin, Y.G., M.W., G.F.).
Guihao ChenDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Meihui WangDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (Q.L., J.Lin, Y.G., M.W., G.F.).
Shangang ZhaoTouchstone Diabetes Center, Department of Internal Medicine (Y.A.A., S.Z., Y.D., P.E.S.), University of Texas Southwestern Medical Center, Dallas.
Chongshan DaiDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Charles D SmartDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Juan LiuDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC (J.Liu, J.W.L.).
Xiang LuoDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Yingfeng DengTouchstone Diabetes Center, Department of Internal Medicine (Y.A.A., S.Z., Y.D., P.E.S.), University of Texas Southwestern Medical Center, Dallas.
Lin TanMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston (L.T., P.L.L.).
Shuang-Jie LvState Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China (S-J.L.).
Shawn M DavidsonKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge (S.M.D., M.G.V.H.).
Jason W LocasaleDepartment of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham, NC (J.Liu, J.W.L.).
Philip L LorenziMetabolomics Core Facility, Department of Bioinformatics and Computational Biology, University of Texas MD Anderson Cancer Center, Houston (L.T., P.L.L.).
Craig R MalloyAdvanced Imaging Research Center (G.S., C.R.M.), University of Texas Southwestern Medical Center, Dallas.
Thomas G GilletteDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Matthew G Vander HeidenKoch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge (S.M.D., M.G.V.H.).
Philipp E SchererTouchstone Diabetes Center, Department of Internal Medicine (Y.A.A., S.Z., Y.D., P.E.S.), University of Texas Southwestern Medical Center, Dallas.
Luke I SzwedaDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
Guosheng FuDepartment of Cardiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (Q.L., J.Lin, Y.G., M.W., G.F.).
Zhao V WangDivision of Cardiology, Department of Internal Medicine (Q.L., C.L., A.E., G.Z., W.M.E., G.C., C.D., C.D.S., X.L., T.G.G., L.I.S., Z.V.W.), University of Texas Southwestern Medical Center, Dallas.
The University of Texas Southwestern Medical Center · USSouthwestern Medical Center · USSir Run Run Shaw Hospital · CNAdvanced Imaging Research (United States) · USDuke University · USThe University of Texas MD Anderson Cancer Center · USChinese Academy of Medical Sciences & Peking Union Medical College · CNDana-Farber Cancer Institute · USMassachusetts Institute of Technology · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI Paula T Hammond · 1985 to 2026
$93.9M
PRE-DOCTORAL TRAINING IN THE BIOLOGICAL SCIENCEST32GM007287 · NIGMS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI BELL, STEPHEN P., KEATING, AMY E · 1985 to 2019
$40.8M
Understanding the role of metabolism in cancerR35CA242379 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI VANDER HEIDEN, MATTHEW G. · 2019 to 2025
$5.8M
American Heart Association-American Stroke Association 14SDG18440002Howard Hughes Medical InstituteNCI NIH HHS P30 CA014051NCI NIH HHS R35 CA242379NIGMS NIH HHS T32 GM007287
6 · The paper itself

Abstract

backgroundMetabolic remodeling precedes most alterations during cardiac hypertrophic growth under hemodynamic stress. The elevation of glucose utilization has been recognized as a hallmark of metabolic remodeling. However, its role in cardiac hypertrophic growth and heart failure in response to pressure overload remains to be fully illustrated. Here, we aimed to dissect the role of cardiac PKM1 (pyruvate kinase muscle isozyme 1) in glucose metabolic regulation and cardiac response under pressure overload.

methodsCardiac-specific deletion of PKM1 was achieved by crossing the floxed PKM1 mouse model with the cardiomyocyte-specific Cre transgenic mouse. PKM1 transgenic mice were generated under the control of tetracycline response elements, and cardiac-specific overexpression of PKM1 was induced by doxycycline administration in adult mice. Pressure overload was triggered by transverse aortic constriction. Primary neonatal rat ventricular myocytes were used to dissect molecular mechanisms. Moreover, metabolomics and nuclear magnetic resonance spectroscopy analyses were conducted to determine cardiac metabolic flux in response to pressure overload.

resultsWe found that PKM1 expression is reduced in failing human and mouse hearts. It is important to note that cardiomyocyte-specific deletion of PKM1 exacerbates cardiac dysfunction and fibrosis in response to pressure overload. Inducible overexpression of PKM1 in cardiomyocytes protects the heart against transverse aortic constriction-induced cardiomyopathy and heart failure. At the mechanistic level, PKM1 is required for the augmentation of glycolytic flux, mitochondrial respiration, and ATP production under pressure overload. Furthermore, deficiency of PKM1 causes a defect in cardiomyocyte growth and a decrease in pyruvate dehydrogenase complex activity at both in vitro and in vivo levels.

conclusionsThese findings suggest that PKM1 plays an essential role in maintaining a homeostatic response in the heart under hemodynamic stress.

Indexed as

Disease SusceptibilityAnimalsBiomarkersCarrier ProteinsCell RespirationDisease Models, AnimalDisease ProgressionEnzyme ActivationGene ExpressionGlucoseGlycolysisHeart FailureHeart Function TestsHumansMembrane ProteinsMiceBiomarkersCarrier ProteinsGlucoseMembrane ProteinsThyroid Hormone-Binding ProteinsThyroid Hormonescardiomegalyglycolysisheart failurepyruvate dehydrogenase complexpyruvate kinase

Identifiers

PMID34102853
PMCPMC8405569
OpenAlexW3171692239

What OpenQuestion 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 OpenQuestion graph.