期刊
FUNDAMENTAL & CLINICAL PHARMACOLOGY
卷 19, 期 6, 页码 661-667出版社
WILEY
DOI: 10.1111/j.1472-8206.2005.00371.x
关键词
human coronary artery; smooth muscle cells; MMP-2 activation; MT1 MMP expression; oxidative radicals; oxidized LDL
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 I 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.
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