Matrix metalloproteinase 9 (MMP-9): The middle-man of post-myocardial infarction extracellular matrix remodeling

Fouad A. Zouein, Ashley DeCoux, Yuan Tian, Jared A. White, Yu Fang Jin, Merry L. Lindsey

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

The substantial involvement of matrix metalloproteinase-9 (MMP-9) in adverse cardiac extracellular matrix (ECM) remodeling makes it one of the most widely investigated MMPs. Mmp-9 functions primarily by directly degrading and activating ECM structural and non-structural molecules to regulate cardiac tissue remodeling. This activity is opposed under physiological conditions by a set of endogenous inhibitors known as tissue inhibitors of metalloproteinases (TIMPS). Following myocardial infarction (MI), this constraint is diminished and MMP-9 tissue and plasma levels acutely increase concomitant with a decline in cardiac function. Mmp-9 loss-of-function experiments in multiple animal models of MI demonstrate an overall beneficial effect and emphasize the importance of MMP-9 inhibition as a therapeutic intervention. This chapter summarizes MMP-9 structure, transcriptional regulation, post-translational modification, and downstream ECM substrates. We also explore the overall important role of MMP-9 in adverse cardiac remodeling post-MI and its potential utility as a pathophysiological biomarker. Finally, we highlight MMP-9 endogenous and pharmacological inhibitors and the challenges that must be overcome to achieve clinical translation. This is a comprehensive review of MMP-9, from its biochemical structure to its potential role in clinical trials, and can serve as an introduction to young researchers who just joined this research area.

Original languageEnglish (US)
Title of host publicationCardiac Fibrosis and Heart Failure
Subtitle of host publicationCause or Effect?
PublisherSpringer International Publishing
Pages237-259
Number of pages23
ISBN (Electronic)9783319174372
ISBN (Print)9783319174365
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Keywords

  • Cardiac remodeling
  • Collagen
  • ECM substrates
  • Inflammation
  • Myocardial infarction
  • Proteomics
  • Scar formation
  • Tissue inhibitors of metalloproteinases

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Zouein, F. A., DeCoux, A., Tian, Y., White, J. A., Jin, Y. F., & Lindsey, M. L. (2015). Matrix metalloproteinase 9 (MMP-9): The middle-man of post-myocardial infarction extracellular matrix remodeling. In Cardiac Fibrosis and Heart Failure: Cause or Effect? (pp. 237-259). Springer International Publishing. https://doi.org/10.1007/978-3-319-17437-2_13