Evidence map›Paper›PMID 32924320›Full record

ArticleMacromolecular bioscience2020

Calcium Signaling Regulates Valvular Interstitial Cell Alignment and Myofibroblast Activation in Fast-Relaxing Boronate Hydrogels.

Hao Ma, Laura J Macdougall, Andrea GonzalezRodriguez, Megan E Schroeder, Dilara Batan, Robert M Weiss, Kristi S Anseth

Abstract read
In one paragraph

Article in Macromolecular bioscience, 2020. 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
–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

23 citing papers in PubMed.

  1. Article
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  8. Review
  9. Article
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  11. Stress relaxation rates of myocardium from failing and non-failing hearts.Biomechanics and modeling in mechanobiology · 2025
    Article
  12. Review
  13. Article
  14. Ion Channels in the Development and Remodeling of the Aortic Valve.International journal of molecular sciences · 2023
    Review
  15. Review
  16. Review
  17. Article
  18. Article
  19. Hydrogel cultures reveal Transient Receptor Potential Vanilloid 4 regulation of myofibroblast activation and proliferation in valvular interstitial cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022
    Article
  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

7 authors.

Hao MaDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
Laura J MacdougallDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
Andrea GonzalezRodriguezDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.
Megan E SchroederThe BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.
Dilara BatanThe BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.
Robert M WeissDivision of Cardiovascular Medicine, University of Iowa, Iowa City, IA, 52242, USA.
Kristi S AnsethDepartment of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, CO, 80303, USA.ORCID 0000-0002-5725-5691

Funding

Propagation and Resolution of Injury in Calcific Aortic Valve DiseaseR01HL142935 · NHLBI · UNIVERSITY OF IOWA · PI WEISS, ROBERT M · 2018 to 2022
$2.3M
Hydrogels to Study Synergistic Effects of Signaling Factors and Matrix Mechanics on Valve Disease ProgressionR01HL132353 · NHLBI · UNIVERSITY OF COLORADO · PI ANSETH, KRISTI S. · 2017 to 2020
$1.4M
NHLBI NIH HHS R01 HL132353NHLBI NIH HHS R01 HL142935
6 · The paper itself

Abstract

The role viscoelasticity in fibrotic disease progression is an emerging area of interest. Here, a fast-relaxing hydrogel system is exploited to investigate potential crosstalk between calcium signaling and mechanotransduction. Poly(ethylene glycol) (PEG) hydrogels containing boronate and triazole crosslinkers are synthesized, with varying ratios of boronate to triazole crosslinks to systematically vary the extent of stress relaxation. Valvular interstitial cells (VICs) encapsulated in hydrogels with the highest levels of stress relaxation (90%) exhibit a spread morphology by day 1 and are highly aligned (80 ± 2%) by day 5. Key myofibroblast markers, including α-smooth muscle actin (αSMA) and collagen 1a1 (COL1A1), are significantly elevated. VIC myofibroblast activation decreases by 42 ± 18% through inhibition of mechanotransduction, independently of VIC morphology and alignment. Calcium signaling through a transient receptor potential vanilloid 4 (TRPV4) is found to regulate VIC spreading, alignment, and activation in a time dependent manner. Inhibition of calcium signaling at early time points results in disturbed cell alignment, decreased mechanotransduction, and diminished activation, while inhibition at later time points only causes partially reduced myofibroblast activation. These results suggest a potential crosstalk mechanism, where calcium signaling acts upstream of mechanosensing and can regulate VIC myofibroblast activation independently of mechanotransduction.

Indexed as

AnimalsCalcium SignalingCollagen Type IFibrosisGene Expression RegulationHumansHydrogelsMechanotransduction, CellularMiceMyofibroblastsPolyethylene GlycolsSwineTriazolesTRPV Cation ChannelsViscoelastic SubstancesCollagen Type IHydrogelsPolyethylene GlycolsTriazolesTRPV Cation ChannelsViscoelastic Substances3D hydrogelsboronate chemistriesmechanotransductionmyofibroblastsvalvular interstitial cells

Identifiers

PMID32924320
PMCPMC7773027

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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.