Fibroblast activation in the infarcted myocardium

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The adult mammalian heart contains abundant fibroblasts. Cardiac fibroblasts are versatile and dynamic cells that not only produce extracellular matrix proteins, but may also serve important functions in myocardial inflammation, angiogenesis and repair. Following injury, cardiac fibroblasts may maintain the integrity of the extracellular matrix network preserving cardiac geometry and function. Myocardial infarction induces dynamic alterations in fibroblast phenotype. During the early stages of infarct healing, cardiac fibroblasts may serve as sentinel cells that sense signals released by dying cardiomyocytes and activate the inflammasome, secreting cytokines and chemokines. During the inflammatory phase, fibroblasts exhibit a matrix-degrading phenotype; myofibroblast conversion may be delayed by activation of Interleukin-1 (IL-1) signaling. Suppression of pro-inflammatory signals and termination of IL-1-driven cascades during the proliferative phase of infarct healing may allow unopposed actions of Transforming Growth Factor (TGF)-β on cardiac fibroblasts, mediating myofibroblast transdifferentiation, matrix synthesis and scar contraction. Angiotensin II, the mast cell proteases chymase and tryptase, growth factors and specialized matrix proteins may co-operate to promote a synthetic and proliferative myofibroblast phenotype. The maturation phase follows, as infarct myofibroblasts cross-link the surrounding matrix, become quiescent and may undergo apoptosis. However, in the non-infarcted remodeling myocardium, fibroblasts may remain activated in response to volume and pressure overload promoting interstitial fibrosis. This chapter discusses the role of cardiac fibroblasts in infarct healing and the mechanisms of their activation, suggesting potential therapeutic targets aimed at attenuating adverse post-infarction remodeling.

Original languageEnglish (US)
Title of host publicationCardiac Fibrosis and Heart Failure: Cause or Effect?
PublisherSpringer International Publishing
Pages5-22
Number of pages18
ISBN (Print)9783319174372, 9783319174365
DOIs
Publication statusPublished - Jan 1 2015

    Fingerprint

Keywords

  • Infarction
  • Ischemia
  • Myofibroblast
  • Proto-myofibroblast
  • Transdifferentiation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Saxena, A., & Frangogiannis, N. G. (2015). Fibroblast activation in the infarcted myocardium. In Cardiac Fibrosis and Heart Failure: Cause or Effect? (pp. 5-22). Springer International Publishing. https://doi.org/10.1007/978-3-319-17437-2_2