Exp Mol Med.
2007 Feb;39(1):106-113.
alpha-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity
- Affiliations
-
- 1Department of Internal Medicine, Keimyung University School of Medicine, Daegu 700-712, Korea. leei@knu.ac.kr
- 2Department of Immunology, Keimyung University School of Medicine, Daegu 700-712, Korea.
- 3Department of Internal Medicine, Ulsan University School of Medicine, Seoul 138-736, Korea.
- 4Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-721, Korea.
Abstract
- 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-kappaB (NF-kappaB) and the consequent up-regulation of matrix metalloproteinase-9 (MMP-9). This study was undertaken to test for a possible effect of alpha-lipoic acid (ALA), a potent inhibitor of NF-kappaB, on MMP-9 expression. ALA inhibited high-glucose- and TNF-alpha-stimulated VSMC migrations in vitro. It also inhibited high-glucose- and TNF-alpha-induced increases in MMP-9 expression. The activity of MMP-9-promoter constructs with mutations in the NF-kappaB binding site was not inhibited by ALA, indicating an involvement of the NF-kappaB 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-kappaB/ MMP-9 pathway, especially with hyperglycemia.