α-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-κB transcriptional activity

• DOI: 10.1038/emm.2007.12
• Publication Date: 2013-01-17T11:55:03Z
• Authors: Hye-Soon Kim; Hye-Jin Kim; Keun-Gyu Park; Yoon-Nyun Kim; Taeg-Kyu Kwon; Joong-Yeol Park; Ki-Up Lee; Jung-Guk Kim; In-Kyu Lee
• Keywords: Male; 0303 health sciences; Thioctic Acid; NF-kappa B; Gene Expression; Muscle, Smooth, Vascular; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Matrix Metalloproteinase 9; Cell Movement; 616; Animals; Promoter Regions, Genetic; Cells, Cultured

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.