Evidence map›Paper›PMID 35128823›Full record

ArticleESC heart failure2022

Mechanosensitive molecular mechanisms of myocardial fibrosis in living myocardial slices.

Raquel Nunez-Toldra, Thomas Kirwin, Elisa Ferraro, Fotios G Pitoulis, Laura Nicastro, Ifigeneia Bardi, Worrapong Kit-Anan, Julia Gorelik, Andre R Simon, Cesare M Terracciano

Open access · goldAbstract read
In one paragraph

Article in ESC heart failure, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
4.6field-weighted citation impact, top 4% 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

23 citing papers in PubMed, 29 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Living myocardial slices as a model for testing cardiac pro-reparative gene therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Review
  8. Review
  9. Review
  10. Article
  11. Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models.International journal of molecular sciences · 2025
    Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
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

10 authors at 2 institutions in 2 countries.

Raquel Nunez-ToldraNational Heart and Lung Institute, Imperial College London, London, UK.ORCID 0000-0002-8716-2138
Thomas KirwinNational Heart and Lung Institute, Imperial College London, London, UK.
Elisa FerraroNational Heart and Lung Institute, Imperial College London, London, UK.
Fotios G PitoulisNational Heart and Lung Institute, Imperial College London, London, UK.
Laura NicastroNational Heart and Lung Institute, Imperial College London, London, UK.
Ifigeneia BardiNational Heart and Lung Institute, Imperial College London, London, UK.
Worrapong Kit-AnanNational Heart and Lung Institute, Imperial College London, London, UK.
Julia GorelikNational Heart and Lung Institute, Imperial College London, London, UK.
Andre R SimonRoyal Brompton and Harefield NHS Foundation Trust, London, UK.
Cesare M TerraccianoNational Heart and Lung Institute, Imperial College London, London, UK.
Lung Institute · USRoyal Brompton & Harefield NHS Foundation Trust · GB

Funding

British Heart Foundation PG/17/61/33187British Heart Foundation PG/20/8/34856British Heart Foundation RG/17/13/33173
6 · The paper itself

Abstract

aimsAltered mechanical load in response to injury is a main driver of myocardial interstitial fibrosis. No current in vitro model can precisely modulate mechanical load in a multicellular environment while maintaining physiological behaviour. Living myocardial slices (LMS) are a 300 μm-thick cardiac preparation with preserved physiological structure and function. Here we apply varying degrees of mechanical preload to rat and human LMS to evaluate early cellular, molecular, and functionality changes related to myocardial fibrosis. METHODS AND

resultsLeft ventricular LMS were obtained from Sprague Dawley rat hearts and human cardiac samples from healthy and failing (dilated cardiomyopathy) hearts. LMS were mounted on custom stretchers and two degrees of diastolic load were applied: physiological sarcomere length (SL) (SL = 2.2 μm) and overload (SL = 2.4 μm). LMS were maintained for 48 h under electrical stimulation in circulating, oxygenated media at 37°C. In overloaded conditions, LMS displayed an increase in nucleus translocation of Yes-associated protein (YAP) and an up-regulation of mechanotransduction markers without loss in cell viability. Expression of fibrotic and inflammatory markers, as well as Collagen I deposition were also observed. Functionally, overloaded LMS displayed lower contractility (7.48 ± 3.07 mN mm

conclusionsThe LMS have a consistent fibrotic remodelling response to pathological load, which can be modulated by a TGF-βR blocker. The LMS platform allows the study of mechanosensitive molecular mechanisms of myocardial fibrosis and can lead to the development of novel therapeutic strategies.

Indexed as

CardiomyopathiesMechanotransduction, CellularAnimalsFibrosisHumansMyocardiumRatsRats, Sprague-DawleyHeart failureMechanical loadMyocardial fibrosisMyocardial slices

Identifiers

PMID35128823
PMCPMC8934971
OpenAlexW4210888062

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.