MMP-9 signaling in the left ventricle following myocardial infarction

Am J Physiol Heart Circ Physiol. 2016 Jul 1;311(1):H190-8. doi: 10.1152/ajpheart.00243.2016. Epub 2016 May 20.

Abstract

Following myocardial infarction (MI), the left ventricle (LV) undergoes a series of cardiac wound healing responses that involve both the stimulation of robust inflammation to clear necrotic myocytes and tissue debris and the induction of extracellular matrix (ECM) protein synthesis to generate an infarct scar. The collective changes in myocardial structure and function are termed LV remodeling, and matrix metalloproteinase-9 (MMP-9) is a key instigator of post-MI LV remodeling. Through direct molecular effects on ECM and inflammatory protein turnover as well as indirect effects on major cell types that coordinate cardiac wound healing, namely the infiltrating leukocytes and the cardiac fibroblasts, MMP-9 coordinates multiple aspects of LV remodeling. In this review, we will discuss recent research that has expanded our understanding of post-MI LV remodeling, including recent proteomic advances focused on the ECM compartment to provide novel functional and translational insights. This overview will summarize how our understanding of MMP-9 has evolved over the last decade and will provide insight into future directions that will drive our understanding of MMP-9-directed cardiac ECM turnover in the post-MI LV.

Keywords: extracellular matrix; matrix metalloproteinases-9; proteomics; signaling; transcription factors.

Publication types

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

MeSH terms

  • Animals
  • Extracellular Matrix / metabolism*
  • Extracellular Matrix / pathology
  • Heart Ventricles / enzymology*
  • Heart Ventricles / pathology
  • Heart Ventricles / physiopathology
  • Humans
  • Inflammation Mediators / metabolism
  • Matrix Metalloproteinase 9 / metabolism*
  • Myocardial Infarction / enzymology*
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Signal Transduction
  • Up-Regulation
  • Ventricular Function, Left*
  • Ventricular Remodeling*
  • Wound Healing*

Substances

  • Inflammation Mediators
  • Matrix Metalloproteinase 9