The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction

Marcin Dobaczewski, Carlos Gonzalez-Quesada, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

310 Citations (Scopus)

Abstract

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)-β 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.

Original languageEnglish (US)
Pages (from-to)504-511
Number of pages8
JournalJournal of Molecular and Cellular Cardiology
Volume48
Issue number3
DOIs
StatePublished - Mar 2010
Externally publishedYes

Fingerprint

Fibronectins
Extracellular Matrix
Myocardial Infarction
Matrix Metalloproteinases
Collagen
Fibroblasts
Thrombospondin 1
Tenascin
Osteopontin
Myofibroblasts
Transforming Growth Factors
Fibrin
Chemokines
Fibrinogen
Cicatrix
Cysteine
Blood Vessels
Signal Transduction
Cell Survival
Proteins

Keywords

  • Chemokines
  • Collagen
  • Cytokine
  • Hyaluronan
  • Matricellular proteins
  • Matrix Metalloproteinases
  • Myocardial infarction
  • Myofibroblast
  • Remodeling
  • TGF-β
  • Wound healing

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. / Dobaczewski, Marcin; Gonzalez-Quesada, Carlos; Frangogiannis, Nikolaos G.

In: Journal of Molecular and Cellular Cardiology, Vol. 48, No. 3, 03.2010, p. 504-511.

Research output: Contribution to journalArticle

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