Exp Mol Med.  2007 Feb;39(1):106-113.

alpha-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity

  • 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.


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.


hyperplasia; matrix metalloproteinase-9; muscle, smooth, vascular; NF-kappaB; thioctic acid; tunica intima; vascular smooth muscle cell

MeSH Terms

Thioctic Acid/*pharmacology
Rats, Sprague-Dawley
Promoter Regions (Genetics)/genetics
NF-kappa B/*metabolism
Muscle, Smooth, Vascular/cytology/drug effects/metabolism
Matrix Metalloproteinase 9/genetics/*metabolism
Gene Expression/*drug effects/*genetics
Cells, Cultured
Cell Movement/drug effects
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