Exp Mol Med.  2007 Feb;39(1):106-113.

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

• Kim HS
• Kim HJ
• Park KG
• Kim YN
• Kwon TK
• Park JY
• Lee KU
• Kim JG
• Lee IK

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.

Keyword

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