Fibroblasts in myocardial infarction: a role in inflammation and repair

J Mol Cell Cardiol. 2014 May;70:74-82. doi: 10.1016/j.yjmcc.2013.11.015. Epub 2013 Dec 7.


Fibroblasts do not only serve as matrix-producing reparative cells, but exhibit a wide range of functions in inflammatory and immune responses, angiogenesis and neoplasia. The adult mammalian myocardium contains abundant fibroblasts enmeshed within the interstitial and perivascular extracellular matrix. The current review manuscript discusses the dynamic phenotypic and functional alterations of cardiac fibroblasts following myocardial infarction. Extensive necrosis of cardiomyocytes in the infarcted heart triggers an intense inflammatory reaction. In the early stages of infarct healing, fibroblasts become pro-inflammatory cells, activating the inflammasome and producing cytokines, chemokines and proteases. Pro-inflammatory cytokines (such as Interleukin-1) delay myofibroblast transformation, until the wound is cleared from dead cells and matrix debris. Resolution of the inflammatory infiltrate is associated with fibroblast migration, proliferation, matrix protein synthesis and myofibroblast conversion. Growth factors and matricellular proteins play an important role in myofibroblast activation during the proliferative phase of healing. Formation of a mature cross-linked scar is associated with clearance of fibroblasts, as poorly-understood inhibitory signals restrain the fibrotic response. However, in the non-infarcted remodeling myocardium, local fibroblasts may remain activated in response to volume and pressure overload and may promote interstitial fibrosis. Considering their abundance, their crucial role in cardiac inflammation and repair, and their involvement in myocardial dysfunction and arrhythmogenesis, cardiac fibroblasts may be key therapeutic targets in cardiac remodeling. This article is part of a Special Issue entitled Myocyte-Fibroblast Signalling in Myocardium.

Keywords: Cardiac remodeling; Extracellular matrix; Fibroblast; Inflammation; Myocardial infarction; Transforming growth factor (TGF)-β.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Movement
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / metabolism
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Fibroblasts / cytology*
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Humans
  • Inflammation / metabolism
  • Inflammation / pathology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Signal Transduction*
  • Wound Healing / physiology*


  • Cytokines
  • Extracellular Matrix Proteins
  • Intercellular Signaling Peptides and Proteins