Myocardial fibroblast-matrix interactions and potential therapeutic targets

J Mol Cell Cardiol. 2014 May:70:92-9. doi: 10.1016/j.yjmcc.2014.01.008. Epub 2014 Jan 26.

Abstract

The cardiac extracellular matrix (ECM) is a dynamic structure, adapting to physiological and pathological stresses placed on the myocardium. Deposition and organization of the matrix fall under the purview of cardiac fibroblasts. While often overlooked compared to myocytes, fibroblasts play a critical role in maintaining ECM homeostasis under normal conditions and in response to pathological stimuli assume an activated, myofibroblast phenotype associated with excessive collagen accumulation contributing to impaired cardiac function. Complete appreciation of fibroblast function is hampered by the lack of fibroblast-specific reagents and the heterogeneity of fibroblast precursors. This is further complicated by our ability to dissect the role of myofibroblasts versus fibroblasts in myocardial in remodeling. This review highlights critical points in the regulation of collagen deposition by fibroblasts, the current panel of molecular tools used to identify fibroblasts and the role of fibroblast-matrix interactions in fibroblast function and differentiation into the myofibroblast phenotype. The clinical potential of exploiting differences between fibroblasts and myofibroblasts and using them to target specific fibroblast populations is also discussed. This article is part of a Special Issue entitled "Myocyte-Fibroblast Signalling in Myocardium."

Keywords: Discoidin Domain Receptor; Extracellular matrix; Fibroblast; Integrin; Myofibroblast; Transformation.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Discoidin Domain Receptors
  • Extracellular Matrix / chemistry
  • Extracellular Matrix / metabolism*
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibrosis / metabolism*
  • Fibrosis / pathology
  • Fibrosis / therapy
  • Gene Expression Regulation
  • Humans
  • Integrins / genetics
  • Integrins / metabolism
  • Molecular Targeted Therapy
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myofibroblasts / metabolism*
  • Myofibroblasts / pathology
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Mitogen / genetics
  • Receptors, Mitogen / metabolism
  • Signal Transduction*

Substances

  • Collagen Type I
  • Integrins
  • Receptors, Mitogen
  • Discoidin Domain Receptors
  • Receptor Protein-Tyrosine Kinases