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Oxidative stress activates MMP‐2 in cultured human coronary smooth muscle cells
Author(s) -
Valentin François,
Bueb JeanLuc,
Kieffer Pascal,
Tschirhart Eric,
Atkinson Jeffrey
Publication year - 2005
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2005.00371.x
Subject(s) - oxidative stress , matrix metalloproteinase , xanthine oxidase , zymography , oxidative phosphorylation , microbiology and biotechnology , chemistry , reactive oxygen species , xanthine , western blot , vascular smooth muscle , atheroma , biochemistry , medicine , endocrinology , biology , enzyme , smooth muscle , gene
Oxidative stress is a cardinal feature of the inflammatory process and is involved in various pathologies including atherosclerosis. One of the important mechanisms in which oxidative stress may play a role is activation of matrix metalloproteinases such as MMP‐2, which are involved in plaque destabilization. We investigated the mechanisms by which oxidative stress induces MMP‐2 activation in cultured human coronary artery smooth muscle cells. Using zymography and Western blot analysis, we showed that oxidized low‐density lipoproteins activate MMP‐2 through up‐regulation of the expression and activation of a membrane‐type 1 matrix metalloproteinase (MT1‐MMP). A second mechanism of MMP‐2 activation involves oxidative radicals generated by the xanthine/xanthine oxidase complex (X/Xo). Research on these two mechanisms of MMP activation could lead to the elaboration of new vascular therapies for the treatment of atheroma based on interruption of a specific oxidative stress pathway.