Document Detail


Mechanical regulation of fibroblast migration and collagen remodelling in healing myocardial infarcts.
MedLine Citation:
PMID:  22495588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Effective management of healing and remodelling after myocardial infarction is an important problem in modern cardiology practice. We have recently shown that the level of infarct anisotropy is a critical determinant of heart function following a large anterior infarction, which suggests that therapeutic gains may be realized by controlling infarct anisotropy. However, factors regulating infarct anisotropy are not well understood. Mechanical, structural and chemical guidance cues have all been shown to regulate alignment of fibroblasts and collagen in vitro, and prior studies have proposed that each of these cues could regulate anisotropy of infarct scar tissue, but understanding of fibroblast behaviour in the complex environment of a healing infarct is lacking. We developed an agent-based model of infarct healing that accounted for the combined influence of these cues on fibroblast alignment, collagen deposition and collagen remodelling. We pooled published experimental data from several sources in order to determine parameter values, then used the model to test the importance of each cue for predicting collagen alignment measurements from a set of recent cryoinfarction experiments. We found that although chemokine gradients and pre-existing matrix structures had important effects on collagen organization, a response of fibroblasts to mechanical cues was critical for correctly predicting collagen alignment in infarct scar. Many proposed therapies for myocardial infarction, such as injection of cells or polymers, alter the mechanics of the infarct region. Our modelling results suggest that such therapies could change the anisotropy of the healing infarct, which could have important functional consequences. This model is therefore a potentially important tool for predicting how such interventions change healing outcomes.
Authors:
Andrew D Rouillard; Jeffrey W Holmes
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-10
Journal Detail:
Title:  The Journal of physiology     Volume:  590     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-09-18     Completed Date:  2013-01-29     Revised Date:  2013-09-17    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  4585-602     Citation Subset:  IM    
Affiliation:
Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Movement / physiology*
Chemokines / physiology
Cicatrix
Collagen / physiology*
Fibroblasts / physiology*
Mechanical Processes
Models, Cardiovascular
Myocardial Infarction*
Rats
Wound Healing / physiology*
Grant Support
ID/Acronym/Agency:
R01 HL-075639/HL/NHLBI NIH HHS; R01 HL075639/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 9007-34-5/Collagen
Comments/Corrections

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