The interaction of extracellular matrix with cells regulates their adhesion, migration and proliferation, and it is believed that damage to vascular matrix components is a factor in the development of atherosclerosis. Evidence has been provided for a role for the haem enzyme MPO (myeloperoxidase), released by activated monocytes (and possibly macrophages), in oxidative events within the artery wall. As MPO is released extracellularly, and is highly basic, it might be expected to associate with poly-anionic matrix components thereby localizing damage to these materials. In this study the reaction of the MPO-derived oxidant hypochlorous acid (HOCl) with extracellular matrix from vascular smooth muscle cells and healthy pig arteries has been examined. HOCl is rapidly consumed by such matrix samples, with the formation of matrix-derived chloramines or chloramides. The yield of these intermediates increases with HOCl dose. These materials undergo a time- and temperature-dependent decay, which parallels the release of sugar and protein components from the treated matrix, consistent with these species being important intermediates. Matrix damage is enhanced by species that increase chloramine/chloramide decomposition, with copper and iron ions being effective catalysts, and decreased by compounds which scavenge chloramines/chloramides, or species derived from them. The effect of such matrix modifications on cellular behaviour is poorly understood, though it is known that changes in matrix materials can have profound effects on cell adhesion, proliferation, growth and phenotype. The observed matrix modifications reported here may therefore modulate cellular behaviour in diseases such as atherosclerosis where MPO-derived oxidants are generated.
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November 2003
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Research Article|
November 15 2003
Fragmentation of extracellular matrix by hypochlorous acid
Alan A. WOODS
;
Alan A. WOODS
The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, New South Wales 2050, Australia
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Michael J. DAVIES
Michael J. DAVIES
1
The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, New South Wales 2050, Australia
1To whom correspondence should be addressed (e-mail m.davies@hri.org.au).
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Biochem J (2003) 376 (1): 219–227.
Article history
Received:
May 15 2003
Revision Received:
July 03 2003
Accepted:
August 11 2003
Accepted Manuscript online:
August 11 2003
Citation
Alan A. WOODS, Michael J. DAVIES; Fragmentation of extracellular matrix by hypochlorous acid. Biochem J 15 November 2003; 376 (1): 219–227. doi: https://doi.org/10.1042/bj20030715
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