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KMID : 0620920070390010106
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Experimental & Molecular Medicine
2007 Volume.39 No. 1 p.106 ~ p.113
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a-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kB transcriptional activity
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Kim Hye-Soon
Kwon Taeg-Kyu
Kim Yoon-Nyun
Lee In-Kyu
Park Joong-Yeol
Lee Ki-Up
Kim Hye-Jin
Park Keun-Gyu
Kim Jung-Guk
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Abstract
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The migration of vascular smooth muscle cells (VSMCs) into the intima, an important step in injury-induced neointimal hyperplasia, requires the activation of nuclear factor-kB (NF-kB) and the consequent up-regulation of matrix metalloproteinase-9 (MMP-9). This study was undertaken to test for a possible effect of a-lipoic acid (ALA), a potent inhibitor of NF-κB, on MMP-9 expression. ALA inhibited high-glucose- and TNF-a-stimulated VSMC migrations in vitro. It also inhibited high-glucose- and TNF-a-induced increases in MMP-9 expression. The activity of MMP-9-promoter constructs with mutations in the NF-kB binding site was not inhibited by ALA, indicating an involvement of the NF-kB signaling pathway in the ALA-specific inhibition of MMP-9. These data suggest the possibility that ALA may be useful for the prevention of neointimal hyperplasia after angioplasty, by inhibiting the NF-kB/ MMP-9 pathway, especially with hyperglycemia.
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KEYWORD
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hyperplasia, matrix metalloproteinase-9, muscle smooth vascular, NF-κB, thioctic acid, tunica intima, vascular smooth muscle cell
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