Document Detail

Type I collagen cleavage is essential for effective fibrotic repair after myocardial infarction.
MedLine Citation:
PMID:  21907695     Owner:  NLM     Status:  MEDLINE    
Efficient deposition of type I collagen is fundamental to healing after myocardial infarction. Whether there is also a role for cleavage of type I collagen in infarct healing is unknown. To test this, we undertook coronary artery occlusion in mice with a targeted mutation (Col1a1(r/r)) that yields collagenase-resistant type I collagen. Eleven days after infarction, Col1a1(r/r) mice had a lower mean arterial pressure and peak left ventricular systolic pressure, reduced ventricular systolic function, and worse diastolic function, compared with wild-type littermates. Infarcted Col1a1(r/r) mice also had greater 30-day mortality, larger left ventricular lumens, and thinner infarct walls. Interestingly, the collagen fibril content within infarcts of mutant mice was not increased. However, circular polarization microscopy revealed impaired collagen fibril organization and mechanical testing indicated a predisposition to scar microdisruption. Three-dimensional lattices of collagenase-resistant fibrils underwent cell-mediated contraction, but the fibrils did not organize into birefringent collagen bundles. In addition, time-lapse microscopy revealed that, although cells migrated smoothly on wild-type collagen fibrils, crawling and repositioning on collagenase-resistant collagen was impaired. We conclude that type I collagen cleavage is required for efficient healing of myocardial infarcts and is critical for both dynamic positioning of collagen-producing cells and hierarchical assembly of collagen fibrils. This seemingly paradoxical requirement for collagen cleavage in fibrotic repair should be considered when designing potential strategies to inhibit matrix degradation in cardiac disease.
Zengxuan Nong; Caroline O'Neil; Ming Lei; Robert Gros; Alanna Watson; Amin Rizkalla; Kibret Mequanint; Shaohua Li; Matthew J Frontini; Qingping Feng; J Geoffrey Pickering
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-09-09
Journal Detail:
Title:  The American journal of pathology     Volume:  179     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-10-31     Completed Date:  2012-01-24     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2189-98     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
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MeSH Terms
Cell Movement
Collagen Type I / genetics,  metabolism*
Collagenases / genetics,  physiology*
Coronary Vessels
Fibroblasts / enzymology*,  physiology
Mice, Inbred C57BL
Mutation / genetics
Myocardial Infarction / enzymology*
Wound Healing / physiology*
Grant Support
//Canadian Institutes of Health Research
Reg. No./Substance:
0/Collagen Type I; 0/collagen type I, alpha 1 chain; EC 3.4.24.-/Collagenases

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