The Living Scar--Cardiac Fibroblasts and the Injured Heart

Trends Mol Med. 2016 Feb;22(2):99-114. doi: 10.1016/j.molmed.2015.12.006. Epub 2016 Jan 14.


Cardiac scars, often dubbed 'dead tissue', are very much alive, with heterocellular activity contributing to the maintenance of structural and mechanical integrity following heart injury. To form a scar, non-myocytes such as fibroblasts are recruited from intra- and extra-cardiac sources. Fibroblasts perform important autocrine and paracrine signaling functions. They also establish mechanical and, as is increasingly evident, electrical junctions with other cells. While fibroblasts were previously thought to act simply as electrical insulators, they may be electrically connected among themselves and, under some circumstances, to other cells including cardiomyocytes. A better understanding of these biophysical interactions will help to target scar structure and function, and will facilitate the development of novel therapies aimed at modifying scar properties for patient benefit.

Keywords: cardiac; fibrosis; non-myocyte.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Autocrine Communication
  • Cell Movement
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Chemokine CXCL10 / genetics
  • Chemokine CXCL10 / metabolism
  • Cicatrix / genetics
  • Cicatrix / metabolism*
  • Cicatrix / pathology
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gap Junctions / metabolism*
  • Gap Junctions / ultrastructure
  • Gene Expression Regulation
  • Heart Injuries / genetics
  • Heart Injuries / metabolism*
  • Heart Injuries / pathology
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Myocytes, Cardiac / metabolism*
  • Myocytes, Cardiac / pathology
  • Paracrine Communication
  • Signal Transduction
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • CCL2 protein, human
  • CXCL10 protein, human
  • Chemokine CCL2
  • Chemokine CXCL10
  • MicroRNAs
  • Transforming Growth Factor beta