Oxidative stress activates MMP-2 in cultured human coronary smooth muscle cells

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.