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. 2003 Apr 21;2003(2):138–148. doi: 10.1155/S1110724303209086

Figure 3.

Figure 3

Gene therapy by overexpression of TIMP-3. Following Ad-mediated gene delivery to vascular smooth muscle cells, TIMP-3 is secreted and is found located with the extracellular matrix (ECM). From here, TIMP-3 is available to exert two distinctly different phenotypes through its metalloproteinase inhibitory effects. (a) Matrix metalloproteinases (MMPs, including collagenases, stromelysins, gelatinases, and membrane-type metalloproteinases [MT-MMPs]) are upregulated following vascular injury. TIMPs, through their native MMP inhibitory activity, are able to bind to and retard pro-MMP-to-active enzyme conversion and combined with the ability to block active MMP activity, matrix proteolysis and hence cell migration is inhibited [45]. (b) TIMP-3, uniquely amongst the TIMP family, is also able to promote smooth muscle cell death through death receptor-induced caspase activation and induction of apoptosis [46]. Micrographs courtesy of Mark Bond, Bristol Heart Institute, UK.