Mechanical control of cardiac myofibroblasts

J Mol Cell Cardiol. 2016 Apr;93:133-42. doi: 10.1016/j.yjmcc.2015.11.025. Epub 2015 Nov 24.

Abstract

Fibroblasts produce and turn over collagenous extracellular matrix as part of the normal adaptive response to increased mechanical load in the heart, e.g. during prolonged exercise. However, chronic overload as a consequence of hypertension or myocardial injury trigger a repair program that culminates in the formation of myofibroblasts. Myofibroblasts are opportunistically activated from various precursor cells that all acquire a phenotype promoting excessive collagen secretion and contraction of the neo-matrix into stiff scar tissue. Stiff fibrotic tissue reduces heart distensibility, impedes pumping and valve function, contributes to diastolic and systolic dysfunction, and affects myocardial electrical transmission, potentially leading to arrhythmia and heart failure. Here, we discuss how mechanical factors, such as matrix stiffness and strain, are feeding back and cooperate with cytokine signals to drive myofibroblast activation. We elaborate on the importance of considering the mechanical boundary conditions in the heart to generate better cell culture models for mechanistic studies of cardiac fibroblast function. Elements of the force transmission and mechanoperception apparatus acting in myofibroblasts are presented as potential therapeutic targets to treat fibrosis.

Keywords: Extracellular matrix; Fibroblast; Fibrosis; Integrin; Mechanical stress; Scar; Stiffness; TGF-β1; α-Smooth muscle actin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Cell Differentiation
  • Cytokines / metabolism
  • Extracellular Matrix
  • Fibrosis
  • Humans
  • Mechanical Phenomena*
  • Mechanotransduction, Cellular*
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Myofibroblasts / cytology*
  • Myofibroblasts / physiology*
  • Phenotype
  • Stress, Mechanical

Substances

  • Biomarkers
  • Cytokines