Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10954238 | Journal of Molecular and Cellular Cardiology | 2009 | 9 Pages |
Abstract
In the human cardiac myofibroblast, MT1-MMP was central to MMP-2 activation and activated MMP-2 necessary for invasion, confirmed by gene silencing. MMP-2 activation was substantially attenuated by hypoxia (PÂ <Â 0.001), paralleled by inhibition of myofibroblast invasion (PÂ <Â 0.05). In contrast, migration was independent of either MT1-MMP or MMP-2. Reduced membrane expression of MT1-MMP (PÂ <Â 0.05) was responsible for the hypoxic reduction of MMP-2 activation, with no change in either total MMP-2 or TIMP-2. In conclusion, hypoxia reduces MMP-2 activation and subsequent invasion of human cardiac myofibroblasts by reducing membrane expression of MT1-MMP and may delay healing after MI. Regulation of these MMPs remains an attractive target for therapeutic intervention.
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Authors
Kirsten Riches, Michael E. Morley, Neil A. Turner, David J. O'Regan, Stephen G. Ball, Chris Peers, Karen E. Porter,