Properties and Functions of Fibroblasts and Myofibroblasts in Myocardial Infarction

Harikrishnan Venugopal, Anis Hanna, Claudio Humeres, Nikolaos G. Frangogiannis

Research output: Contribution to journalReview articlepeer-review

Abstract

The adult mammalian heart contains abundant interstitial and perivascular fibroblasts that expand following injury and play a reparative role but also contribute to maladaptive fibrotic remodeling. Following myocardial infarction, cardiac fibroblasts undergo dynamic phenotypic transitions, contributing to the regulation of inflammatory, reparative, and angiogenic responses. This review manuscript discusses the mechanisms of regulation, roles and fate of fibroblasts in the infarcted heart. During the inflammatory phase of infarct healing, the release of alarmins by necrotic cells promotes a pro-inflammatory and matrix-degrading fibroblast phenotype that may contribute to leukocyte recruitment. The clearance of dead cells and matrix debris from the infarct stimulates anti-inflammatory pathways and activates transforming growth factor (TGF)-β cascades, resulting in the conversion of fibroblasts to α-smooth muscle actin (α-SMA)-expressing myofibroblasts. Activated myofibroblasts secrete large amounts of matrix proteins and form a collagen-based scar that protects the infarcted ventricle from catastrophic complications, such as cardiac rupture. Moreover, infarct fibroblasts may also contribute to cardiac repair by stimulating angiogenesis. During scar maturation, fibroblasts disassemble α-SMA+ stress fibers and convert to specialized cells that may serve in scar maintenance. The prolonged activation of fibroblasts and myofibroblasts in the infarct border zone and in the remote remodeling myocardium may contribute to adverse remodeling and to the pathogenesis of heart failure. In addition to their phenotypic plasticity, fibroblasts exhibit remarkable heterogeneity. Subsets with distinct phenotypic profiles may be responsible for the wide range of functions of fibroblast populations in infarcted and remodeling hearts.

Original languageEnglish (US)
Article number1386
JournalCells
Volume11
Issue number9
DOIs
StatePublished - May 1 2022

Keywords

  • angiogenesis
  • cytokine
  • extracellular matrix
  • fibroblast
  • fibrosis
  • myocardial infarction
  • myofibroblast
  • remodeling

ASJC Scopus subject areas

  • Medicine(all)

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