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 language | English (US) |
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Title of host publication | Cardiac Fibrosis and Heart Failure |
Subtitle of host publication | Cause or Effect? |
Publisher | Springer International Publishing |
Pages | 237-259 |
Number of pages | 23 |
ISBN (Electronic) | 9783319174372 |
ISBN (Print) | 9783319174365 |
DOIs | |
State | Published - Jan 1 2015 |
Externally published | Yes |
Keywords
- Cardiac remodeling
- Collagen
- ECM substrates
- Inflammation
- Myocardial infarction
- Proteomics
- Scar formation
- Tissue inhibitors of metalloproteinases
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- General Medicine