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Fragmentation of extracellular matrix by hypochlorous acid
Alan A Woods1, Michael J Davies
1The Heart Research Institute, 145 Missenden Road, Camperdown, Sydney, New South Wales 2050, Australia.
The Biochemical Journal
|August 13, 2003
Summary
Myeloperoxidase (MPO) oxidants damage artery wall extracellular matrix. This study shows MPO-derived hypochlorous acid forms chloramines in matrix, leading to matrix breakdown and potentially influencing atherosclerosis progression.
Area of Science:
- Biochemistry
- Vascular Biology
- Pathology
Background:
- Extracellular matrix (ECM) interactions regulate cell behavior; ECM damage contributes to atherosclerosis.
- Myeloperoxidase (MPO), an enzyme released by monocytes/macrophages, is implicated in arterial oxidative stress.
- MPO's basic nature suggests it binds ECM, localizing oxidative damage.
Purpose of the Study:
- To investigate the reaction of MPO-derived hypochlorous acid (HOCl) with vascular ECM.
- To characterize the formation and decay of HOCl-induced modifications in ECM.
- To understand how these modifications might impact cellular behavior in diseases like atherosclerosis.
Main Methods:
- Incubation of vascular ECM with HOCl.
- Analysis of HOCl consumption and formation of matrix-derived chloramines/chloramides.
- Investigation of chloramine/chloramide decay kinetics and factors influencing it (e.g., metal ions, scavengers).
Main Results:
- HOCl rapidly consumed by ECM, forming matrix-derived chloramines/chloramides.
- Yield of chloramines/chloramides increased with HOCl dose.
- Chloramine/chloramide decay was time- and temperature-dependent, releasing matrix components and was catalyzed by copper and iron ions.
Conclusions:
- MPO-derived HOCl modifies vascular ECM by forming chloramines/chloramides.
- The decay of these modified species leads to matrix degradation.
- These ECM modifications may alter cellular behavior, contributing to atherosclerosis pathogenesis.