Fig. 4

The mechanisms of MMP-9 in ischemic heart disease. The most common pathway for MMP-9 activation is hydrolytic proto-domains of other proteases such as MMP1, 2, 3, 7, or 13, cathepsin, and plasminogen. MMP-9 can also be activated by post-translational modifications of the domain cysteine residues, including S-glutathionylation or S-nitrosylation. The substrates of MMP-9 include ECM proteins (e.g. collagen, fibronectin, laminin, thrombo-reactive protein, and tendon in C), non-ECM substrates (various cytokines and chemokines, such as TNFα, IL-1β, TGFβ, and CXC motif ligands), and novel substrates (e.g. CD36 and citrate synthase). Thus, MMP-9 plays an essential role in ischemic heart disease by regulating macrophage phagocytosis, neutrophil apoptosis, inflammation, fibrosis, and angiogenesis. MMP matrix metalloproteinases, MI myocardial infarction, ECM extracellular matrix, TGF-β transforming growth factor β, VEGF vascular endothelial growth factor