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.
Valentin
François
F
Centre de Recherche Public-Santé, L-1511 Luxembourg, Grand-Duché du Luxembourg.
Bueb
Jean-Luc
JL
Kieffer
Pascal
P
Tschirhart
Eric
E
Atkinson
Jeffrey
J
D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation; D004790:Enzyme Induction; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology*; D018384:Oxidative Stress
D020778:Matrix Metalloproteinase 2