Fibroblasts in post-infarction inflammation and cardiac repair

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

Fibroblasts are the predominant cell type in the cardiac interstitium. As the main matrix-producing cells in the adult mammalian heart, fibroblasts maintain the integrity of the extracellular matrix network, thus preserving geometry and function. Following myocardial infarction fibroblasts undergo dynamic phenotypic alterations and direct the reparative response. Due to their strategic location, cardiac fibroblasts serve as sentinel cells that sense injury and activate the inflammasome secreting cytokines and chemokines. During the proliferative phase of healing, infarct fibroblasts undergo myofibroblast transdifferentiation forming stress fibers and expressing contractile proteins (such as α-smooth muscle actin). Mechanical stress, transforming growth factor (TGF)-β/Smad3 signaling and alterations in the composition of the extracellular matrix induce acquisition of the myofibroblast phenotype. In the highly cellular and growth factor-rich environment of the infarct, activated myofibroblasts produce matrix proteins, proteases and their inhibitors regulating matrix metabolism. As the infarct matures, "stress-shielding" of myofibroblasts by the cross-linked matrix and growth factor withdrawal may induce quiescence and ultimately cause apoptotic death. Because of their critical role in post-infarction cardiac remodeling, fibroblasts are promising therapeutic targets following myocardial infarction. However, the complexity of fibroblast functions and the pathophysiologic heterogeneity of post-infarction remodeling in the clinical context discourage oversimplified approaches in clinical translation. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction.

Original languageEnglish (US)
Pages (from-to)945-953
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1833
Issue number4
DOIs
StatePublished - Apr 2013

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Infarction
Fibroblasts
Inflammation
Myofibroblasts
Extracellular Matrix
Intercellular Signaling Peptides and Proteins
Myocardial Infarction
Inflammasomes
Contractile Proteins
Stress Fibers
Mechanical Stress
Transforming Growth Factors
Protease Inhibitors
Chemokines
Cardiac Myocytes
Smooth Muscle
Actins
Cause of Death
Cytokines
Phenotype

Keywords

  • Cardiac remodeling
  • Extracellular matrix
  • Fibroblast
  • Growth factors
  • Inflammation
  • TGF-β

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Fibroblasts in post-infarction inflammation and cardiac repair. / Chen, Wei; Frangogiannis, Nikolaos G.

In: Biochimica et Biophysica Acta - Molecular Cell Research, Vol. 1833, No. 4, 04.2013, p. 945-953.

Research output: Contribution to journalArticle

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