Document Detail

MT1-MMP-dependent remodeling of cardiac extracellular matrix structure and function following myocardial infarction.
MedLine Citation:
PMID:  22464947     Owner:  NLM     Status:  MEDLINE    
The myocardial extracellular matrix (ECM), an interwoven meshwork of proteins, glycoproteins, proteoglycans, and glycosaminoglycans that is dominated by polymeric fibrils of type I collagen, serves as the mechanical scaffold on which myocytes are arrayed for coordinated and synergistic force transduction. Following ischemic injury, cardiac ECM remodeling is initiated via localized proteolysis, the bulk of which has been assigned to matrix metalloproteinase (MMP) family members. Nevertheless, the key effector(s) of myocardial type I collagenolysis both in vitro and in vivo have remained unidentified. In this study, using cardiac explants from mice deficient in each of the major type I collagenolytic MMPs, including MMP-13, MMP-8, MMP-2, MMP-9, or MT1-MMP, we identify the membrane-anchored MMP, MT1-MMP, as the dominant collagenase that is operative within myocardial tissues in vitro. Extending these observations to an in vivo setting, mice heterozygous for an MT1-MMP-null allele display a distinct survival advantage and retain myocardial function relative to wild-type littermates in an experimental model of myocardial infarction, effects associated with preservation of the myocardial type I collagen network as a consequence of the decreased collagenolytic potential of cardiac fibroblasts. This study identifies MT1-MMP as a key MMP responsible for effecting postinfarction cardiac ECM remodeling and cardiac dysfunction.
Gerald C Koenig; R Grant Rowe; Sharlene M Day; Farideh Sabeh; Jeffrey J Atkinson; Kenneth R Cooke; Stephen J Weiss
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-29
Journal Detail:
Title:  The American journal of pathology     Volume:  180     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-27     Completed Date:  2012-08-06     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1863-78     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.
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MeSH Terms
Collagen Type I / metabolism
Extracellular Matrix / enzymology*,  physiology
Fibroblasts / enzymology
In Situ Hybridization
Matrix Metalloproteinase 14 / deficiency,  physiology*
Mice, Inbred C57BL
Mice, Knockout
Myocardial Infarction / enzymology*,  pathology,  physiopathology,  ultrasonography
Myocardial Ischemia / metabolism,  ultrasonography
Organ Culture Techniques
Ventricular Remodeling / physiology*
Grant Support
Reg. No./Substance:
0/Collagen Type I; EC Metalloproteinase 14

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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