Document Detail


The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction.
MedLine Citation:
PMID:  19631653     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The dynamic alterations in the cardiac extracellular matrix following myocardial infarction not only determine the mechanical properties of the infarcted heart, but also directly modulate the inflammatory and reparative response. During the inflammatory phase of healing, rapid activation of Matrix Metalloproteinases (MMP) causes degradation of the cardiac extracellular matrix. Matrix fragments exert potent pro-inflammatory actions, while MMPs process cytokines and chemokines altering their biological activity. In addition, vascular hyperpermeability results in extravasation of fibronectin and fibrinogen leading to formation of a plasma-derived provisional matrix that serves as a scaffold for leukocyte infiltration. Clearance of the infarct from dead cells and matrix debris is essential for resolution of inflammation and marks the transition to the proliferative phase. The fibrin-based provisional matrix is lysed and cellular fibronectin is secreted. ED-A fibronectin, mechanical tension and Transforming Growth Factor (TGF)-beta are essential for modulation of fibroblasts into myofibroblasts, the main collagen-secreting cells in the wound. The matricellular proteins thrombospondin-1 and -2, osteopontin, tenascin-C, periostin, and secreted protein acidic and rich in cysteine (SPARC) are induced in the infarct regulating cellular interactions and promoting matrix organization. As the infarct matures, matrix cross-linking results in formation of a dense collagen-based scar. At this stage, shielding of fibroblasts from external mechanical tension by the mature matrix network may promote deactivation and cellular quiescence. The components of the extracellular matrix do not passively follow the pathologic alterations of the infarcted heart but critically modulate inflammatory and reparative pathways by transducing signals that affect cell survival, phenotype and gene expression.
Authors:
Marcin Dobaczewski; Carlos Gonzalez-Quesada; Nikolaos G Frangogiannis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review     Date:  2009-07-23
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  48     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-05-14     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  504-11     Citation Subset:  IM    
Copyright Information:
2009 Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Extracellular Matrix / metabolism*
Humans
Matrix Metalloproteinases / metabolism
Models, Biological
Myocardial Infarction / metabolism*,  physiopathology
Wound Healing / physiology
Grant Support
ID/Acronym/Agency:
R01 HL-76246/HL/NHLBI NIH HHS; R01 HL-85440/HL/NHLBI NIH HHS; R01 HL076246/HL/NHLBI NIH HHS; R01 HL076246-05/HL/NHLBI NIH HHS; R01 HL085440/HL/NHLBI NIH HHS; R01 HL085440-02/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
EC 3.4.24.-/Matrix Metalloproteinases
Comments/Corrections

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