Aging and the Cardiac Collagen Matrix: Novel Mediators of Fibrotic Remodelling

J Mol Cell Cardiol. 2016 Apr;93:175-85. doi: 10.1016/j.yjmcc.2015.11.005. Epub 2015 Nov 11.

Abstract

Cardiovascular disease is a leading cause of death worldwide and there is a pressing need for new therapeutic strategies to treat such conditions. The risk of developing cardiovascular disease increases dramatically with age, yet the majority of experimental research is executed using young animals. The cardiac extracellular matrix (ECM), consisting predominantly of fibrillar collagen, preserves myocardial integrity, provides a means of force transmission and supports myocyte geometry. Disruptions to the finely balanced control of collagen synthesis, post-synthetic deposition, post-translational modification and degradation may have detrimental effects on myocardial functionality. It is now well established that the aged heart is characterized by fibrotic remodelling, but the mechanisms responsible for this are incompletely understood. Furthermore, studies using aged animal models suggest that interstitial remodelling with disease may be age-dependent. Thus with the identification of new therapeutic strategies targeting fibrotic remodelling, it may be necessary to consider age-dependent mechanisms. In this review, we discuss remodelling of the cardiac collagen matrix as a function of age, whilst highlighting potential novel mediators of age-dependent fibrotic pathways.

Keywords: Aging; Collagen; Extracellular matrix; Fibrosis; Heart failure.

Publication types

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

MeSH terms

  • Aging / metabolism*
  • Animals
  • Biomarkers
  • Collagen / metabolism*
  • Extracellular Matrix / metabolism*
  • Fibrosis
  • Humans
  • Matrix Metalloproteinases / metabolism
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Protein Processing, Post-Translational
  • Tissue Inhibitor of Metalloproteinases / metabolism
  • Ventricular Dysfunction / etiology
  • Ventricular Dysfunction / metabolism
  • Ventricular Dysfunction / pathology
  • Ventricular Dysfunction / physiopathology
  • Ventricular Remodeling

Substances

  • Biomarkers
  • Tissue Inhibitor of Metalloproteinases
  • Collagen
  • Matrix Metalloproteinases