Evidence map›Paper›PMID 34019816›Full record

ArticleStem cell reports2021

Increased tissue stiffness triggers contractile dysfunction and telomere shortening in dystrophic cardiomyocytes.

Alex C Y Chang, Gaspard Pardon, Andrew C H Chang, Haodi Wu, Sang-Ging Ong, Asuka Eguchi, Sara Ancel, Colin Holbrook, John Ramunas, Alexandre J S Ribeiro and 11 more

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

Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

26 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
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  5. Stress relaxation rates of myocardium from failing and non-failing hearts.Biomechanics and modeling in mechanobiology · 2025
    Article
  6. Cardiac disease mechanobiology: advances using hiPSC-CMs.Frontiers in cardiovascular medicine · 2025
    Review
  7. Review
  8. Article
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  14. Review
  15. Delivery of mitochondria confers cardioprotection through mitochondria replenishment and metabolic compliance.Molecular therapy : the journal of the American Society of Gene Therapy · 2023
    Article
  16. Article
  17. Review
  18. Review
  19. Article
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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

21 authors at 7 institutions in 3 countries.

Alex C Y ChangDepartment of Cardiology and Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, A419, Bldg #2, 115 Jinzun Road, Pudong New District, Shanghai 200125, China; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: alexchang@shsmu.edu.cn.
Gaspard PardonBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Departments of Bioengineering and Mechanical Engineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA; Mechanical Engineering and Biomolecular Science and Engineering, University of California, Santa Barbara, CA, USA.
Andrew C H ChangBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA; Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Haodi WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Sang-Ging OngStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Asuka EguchiBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA.
Sara AncelBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA.
Colin HolbrookBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA.
John RamunasBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA.
Alexandre J S RibeiroStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Departments of Bioengineering and Mechanical Engineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.
Edward L LaGoryDivision of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
Honghui WangDepartment of Cardiology and Shanghai Institute of Precision Medicine, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, A419, Bldg #2, 115 Jinzun Road, Pudong New District, Shanghai 200125, China.
Kassie KoleckarBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA.
Amato GiacciaDivision of Radiation and Cancer Biology, Department of Radiation Oncology, Stanford University, Stanford, CA, USA.
David L MackDepartment of Rehabilitation Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Martin K ChildersDepartment of Rehabilitation Medicine, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Chris DenningDivision of Cancer & Stem Cells, Biodiscovery Institute, University of Nottingham, University Park NG7 2RD, UK.
John W DayDepartment of Neurology, Stanford University, Stanford, CA, USA.
Joseph C WuStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
Beth L PruittStanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA; Departments of Bioengineering and Mechanical Engineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA; Mechanical Engineering and Biomolecular Science and Engineering, University of California, Santa Barbara, CA, USA.
Helen M BlauBaxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CCSR Room 4215, 269 Campus Drive, Stanford, CA 94305-5175, USA; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. Electronic address: hblau@stanford.edu.
Stanford University · USBaxter (United States) · USCardiovascular Institute of the South · USUniversity of Washington · USShanghai Jiao Tong University · CNUniversity of California, Santa Barbara · USUniversity of Nottingham · GB

Funding

The Impact of Mitochondrial Repression and Lipid Accumulation by HIF on Tumor GrowthR35CA197713 · NCI · STANFORD UNIVERSITY · PI GIACCIA, AMATO J. · 2015 to 2021
$5.3M
Telomere extension using nucleoside-modified mRNA and exosomes as a novel therapeR01AR063963 · NIAMS · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2012 to 2016
$4.3M
Safe, Rapid Telomere Extension to Prevent and Treat HypertensionR21AG044815 · NIA · STANFORD UNIVERSITY · PI BLAU, HELEN M · 2013 to 2014
$434k
British Heart Foundation PG/14/59/ 31000British Heart Foundation RG/14/1/30588British Heart Foundation RG/15/6/31436British Heart Foundation SP/15/9/31605CIHR 201411MFE-338745-169197Medical Research Council G0801098Medical Research Council MR/M017354/1NCI NIH HHS R35 CA197713NIAMS NIH HHS R01 AR063963NIA NIH HHS R21 AG044815
6 · The paper itself

Abstract

Duchenne muscular dystrophy (DMD) is a rare X-linked recessive disease that is associated with severe progressive muscle degeneration culminating in death due to cardiorespiratory failure. We previously observed an unexpected proliferation-independent telomere shortening in cardiomyocytes of a DMD mouse model. Here, we provide mechanistic insights using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Using traction force microscopy, we show that DMD hiPSC-CMs exhibit deficits in force generation on fibrotic-like bioengineered hydrogels, aberrant calcium handling, and increased reactive oxygen species levels. Furthermore, we observed a progressive post-mitotic telomere shortening in DMD hiPSC-CMs coincident with downregulation of shelterin complex, telomere capping proteins, and activation of the p53 DNA damage response. This telomere shortening is blocked by blebbistatin, which inhibits contraction in DMD cardiomyocytes. Our studies underscore the role of fibrotic stiffening in the etiology of DMD cardiomyopathy. In addition, our data indicate that telomere shortening is progressive, contraction dependent, and mechanosensitive, and suggest points of therapeutic intervention.

Indexed as

BiomarkersCardiomyopathiesCell DifferentiationCells, CulturedCellular MicroenvironmentCulture Media, ConditionedFibrosisFluorescent Antibody TechniqueGene ExpressionHumansImmunophenotypingInduced Pluripotent Stem CellsMechanical PhenomenaMuscular DystrophiesMuscular Dystrophy, DuchenneMyocardial ContractionBiomarkersCulture Media, Conditioneddilated cardiomyopathyDMDfibrosishiPSC-CMtelomere

Identifiers

PMID34019816
PMCPMC8452491
OpenAlexW3160739477

What OpenQuestion holds

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LicenceCC BY
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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.