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Review
. 2013 Nov;28(6):391-403.
doi: 10.1152/physiol.00029.2013.

Matrix metalloproteinase-9: Many shades of function in cardiovascular disease

Andriy Yabluchanskiy  1 , Yonggang Ma, Rugmani Padmanabhan Iyer, Michael E Hall, Merry L Lindsey
Affiliations
Review

Matrix metalloproteinase-9: Many shades of function in cardiovascular disease

Andriy Yabluchanskiy et al. Physiology (Bethesda). 2013 Nov.

Abstract

Matrix metalloproteinase (MMP)-9, one of the most widely investigated MMPs, regulates pathological remodeling processes that involve inflammation and fibrosis in cardiovascular disease. MMP-9 directly degrades extracellular matrix (ECM) proteins and activates cytokines and chemokines to regulate tissue remodeling. MMP-9 deletion or inhibition has proven overall beneficial in multiple animal models of cardiovascular disease. As such, MMP-9 expression and activity is a common end point measured. MMP-9 cell-specific overexpression, however, has also proven beneficial and highlights the fact that little information is available on the underlying mechanisms of MMP-9 function. In this review, we summarize our current understanding of MMP-9 physiology, including structure, regulation, activation, and downstream effects of increased MMP-9. We discuss MMP-9 roles during inflammation and fibrosis in cardiovascular disease. By concentrating on the substrates of MMP-9 and their roles in cardiovascular disease, we explore the overall function and discuss future directions on the translational potential of MMP-9 based therapies.

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Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the author(s).

Figures

FIGURE 1.
FIGURE 1.
Schematic representation of neutrophil roles in inflammation and MMP-9 release
FIGURE 2.
FIGURE 2.
Schematic representation of macrophage roles in inflammation and MMP-9 release
FIGURE 3.
FIGURE 3.
Schematic representation of the cells involved in the post-MI inflammatory and wound-healing process
FIGURE 4.
FIGURE 4.
MMP-9 structure and factors regulating MMP-9 transcription and translation Ets, E-26 transcription factor; NF-κB, nuclear factor κB; PEA-3, polyomavirus enhancer A-binding protein-3; AP-1, activator protein 1; SAF-1, serum amyloid A-activating factor 1; HSP60, heat shock protein 60; TIMP, tissue inhibitor of metalloproteinase; uPA, urokinase plasminogen activator.
FIGURE 5.
FIGURE 5.
Schematic representation of MMP-9 involvement in hypertension
FIGURE 6.
FIGURE 6.
Schematic representations of MMP-9 involvement Schematic representation of MMP-9 involvement in the atherosclerosis (A) and MI (B).
See this image and copyright information in PMC

Comment in

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