Evidence map›Paper›PMID 21306921›Full record

ArticleCardiovascular pathology : the official journal of the Society for Cardiovascular Pathology

Reduced serum content and increased matrix stiffness promote the cardiac myofibroblast transition in 3D collagen matrices.

Peter A Galie, Margaret V Westfall, Jan P Stegemann

Open access · greenAbstract read
In one paragraph

Article in Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
6.5field-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

40 citing papers in PubMed, 67 citations in OpenAlex.

  1. Article
  2. Dressed in Collagen: 2D and 3D Cardiac Fibrosis Models.International journal of molecular sciences · 2025
    Review
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  13. Targeting the renin-angiotensin-aldosterone system in fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2020
    Review
  14. 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

3 authors at 1 institution in 1 country.

Peter A GalieDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
Margaret V Westfall
Jan P Stegemann
University of Michigan–Ann Arbor · US

Funding

Microfluidics in Biomedical Sciences Training ProgramT32EB005582 · NIBIB · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI FAN, XUDONG · 2005 to 2020
$3.9M
NIBIB NIH HHS T32 EB005582
6 · The paper itself

Abstract

introductionThe fibroblast-myofibroblast transition is an important event in the development of cardiac fibrosis and scar formation initiated after myocardial ischemia. The goals of the present study were to better understand the contribution of environmental factors to this transition and determine whether myofibroblasts provide equally important feedback to the surrounding environment.

methodsThe influence of matrix stiffness and serum concentration on the myofibroblast transition was assessed by measuring message levels of a panel of cardiac fibroblast phenotype markers using quantitative reverse transcriptase polymerase chain reaction. Cell-mediated gel compaction measured the influence of environmental factors on cardiac fibroblast contractility. Immunohistochemistry characterized alpha-smooth muscle actin expression and cell morphology, while static and dynamic compression testing evaluated the effect of the cell response on the mechanical properties of the cell-seeded collagen hydrogels.

resultsBoth reduced serum content and increased matrix stiffness contributed to the myofibroblast transition, as indicated by contractile compaction of the gels, increased message levels of col3α1 and alpha-smooth muscle actin, and a less stellate morphology. However, the effects of serum and matrix stiffness were not additive. Mechanical testing indicated that reduced serum content increased the initial elastic modulus of cell-seeded gels and that gels lost their viscous character with time.

conclusionsThe results suggest that reduced serum and increased matrix stiffness promote the myofibroblast phenotype in the myocardium. This transition both enhances and is promoted by matrix stiffness, indicating the presence of positive feedback that may contribute to the pathogenesis of cardiac fibrosis.

Indexed as

Cell TransdifferentiationActinsAnimalsAnimals, NewbornCell Culture TechniquesCells, CulturedCell ShapeCollagenCulture MediaElastic ModulusFeedback, PhysiologicalFibroblastsFibrosisGene Expression RegulationGenetic MarkersHydrogelsActa2 protein, ratActinsCollagenCulture MediaGenetic MarkersHydrogelsRNA, MessengerTransforming Growth Factor beta

Identifiers

PMID21306921
PMCPMC3110608
OpenAlexW1996738380

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.