Alpha-lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity.
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.
Kim
Hye-Soon
HS
Department of Internal Medicine, Keimyung University School of Medicine, Daegu 700-712, Korea.
Kim
Hye-Jin
HJ
Park
Keun-Gyu
KG
Kim
Yoon-Nyun
YN
Kwon
Taeg-Kyu
TK
Park
Joong-Yeol
JY
Lee
Ki-Up
KU
Kim
Jung-Guk
JG
Lee
In-Kyu
IK
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression / Q000187:drug effects* / Q000235:genetics*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*
D016328:NF-kappa B; D008063:Thioctic Acid; D020780:Matrix Metalloproteinase 9