Evidence mapPaperPMID 40934290Full record

ArticleScience (New York, N.Y.)2025

Preventing hypocontractility-induced fibroblast expansion alleviates dilated cardiomyopathy.

Ross C Bretherton, Isabella M Reichardt, Kristin A Zabrecky, Abigail Nagle, Logan R J Bailey, Darrian Bugg, Sasha Smolgovsky, Amy L Gifford, Timothy S McMillen, Alex J Goldstein and 12 more

Erratum issuedAbstract read
In one paragraph

Article in Science (New York, N.Y.), 2025. 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 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Interstitial cells and arrhythmia.American journal of physiology. Cell physiology · 2026
    Review
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors.

Ross C BrethertonDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0002-9567-8556
Isabella M ReichardtDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0001-5637-8166
Kristin A ZabreckyInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0009-0009-4832-8906
Abigail NagleDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0002-6200-8628
Logan R J BaileyInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0001-7811-7362
Darrian BuggInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-0930-6175
Sasha SmolgovskyInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7735-9922
Amy L GiffordInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0009-0007-8773-0346
Timothy S McMillenDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0001-5261-3229
Alex J GoldsteinInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Kristina B KooikerInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0003-1817-9080
Galina V FlintDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0003-3993-5156
Amy MartinsonInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0009-0008-5797-4689
Jagdambika GunajeInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Franziska KoserInstitute of Physiology II, University of Münster, Münster, Germany.ORCID 0009-0008-9585-0935
Elizabeth PlasterInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.
Wolfgang A LinkeInstitute of Physiology II, University of Münster, Münster, Germany.ORCID 0000-0003-0801-3773
Michael RegnierDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0001-5437-9851
Farid Moussavi-HaramiInstitute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, WA, USA.ORCID 0000-0002-0189-7214
Nathan J SniadeckiDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0001-6960-4492
Cole A DeForestDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0003-0337-3577
Jennifer DavisDepartment of Bioengineering, University of Washington, Seattle, WA, USA.ORCID 0000-0003-2380-1321

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · 1986 to 2025
$12.6M
Vision Research CoreP30EY001730 · UNIVERSITY OF WASHINGTON · 1985 to 2025
$5.1M
Nutrition, Obesity and Atherosclerosis Training ProgramT32HL007028 · NHLBI · UNIVERSITY OF WASHINGTON · 1985 to 2025
$1.9M
UW Center for Translational Muscle ResearchP30AR074990 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$789k
Uncovering The Mechanogenomic Basis For Cardiac PlasticityR01HL142624 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$652k
Regulators of Myofibroblast State Stability & Fibrotic Responsiveness of the HeartR01HL162229 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$635k
Integrating Transcriptome Reprogramming Into Cardiac Plasticity Regulatory MechanismsR01HL141187 · UNIVERSITY OF WASHINGTON · 2025 to 2025
$610k
NEI NIH HHS P30 EY001730NHLBI NIH HHS R01 HL141187NHLBI NIH HHS R01 HL142624NHLBI NIH HHS R01 HL146868NHLBI NIH HHS R01 HL149734NHLBI NIH HHS R01 HL162229NHLBI NIH HHS T32 HL007028NIAMS NIH HHS P30 AR074990NIDDK NIH HHS P30 DK017047NIGMS NIH HHS R35 GM138036NIGMS NIH HHS RM1 GM131981
6 · The paper itself

Abstract

Cardiomyocyte hypocontractility underlies inherited dilated cardiomyopathy (DCM). Yet, whether fibroblasts modify DCM phenotypes remains unclear despite their regulation of fibrosis, which strongly predicts disease severity. Expression of a hypocontractility-linked sarcomeric variant in mice triggered cardiac fibroblast expansion from the de novo formation of hyperproliferative mechanosensitized fibroblast states, which occurred prior to eccentric myocyte remodeling. Initially, this fibroblast response reorganized fibrillar collagen and stiffened the myocardium, albeit without depositing fibrotic tissue. These adaptations coincided with heightened matrix-integrin receptor interactions and diastolic tension sensation at focal adhesions within fibroblasts. Targeted p38 deletion arrested these cardiac fibroblast responses in DCM mice, which prevented cardiomyocyte remodeling and improved contractility. p38-mediated fibroblast responses were essential regulators of DCM severity, marking a potential cellular target for therapeutic intervention.

Indexed as

Cardiomyopathy, DilatedFibroblastsMyocardial ContractionMyocytes, CardiacAnimalsCell ProliferationFibrosisFocal AdhesionsGene DeletionIntegrinsMiceMyocardiump38 Mitogen-Activated Protein KinasesSarcomeresIntegrinsp38 Mitogen-Activated Protein Kinases

Identifiers

PMID40934290
PMCPMC12863455

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.