alpha-Lipoic acid inhibits matrix metalloproteinase-9 expression by inhibiting NF-kappaB transcriptional activity.
- Author:
Hye Soon KIM
1
;
Hye Jin KIM
;
Keun Gyu PARK
;
Yoon Nyun KIM
;
Taeg Kyu KWON
;
Joong Yeol PARK
;
Ki Up LEE
;
Jung Guk KIM
;
In Kyu LEE
Author Information
1. Department of Internal Medicine, Keimyung University School of Medicine, Daegu 700-712, Korea. leei@knu.ac.kr
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords:
hyperplasia;
matrix metalloproteinase-9;
muscle, smooth, vascular;
NF-kappaB;
thioctic acid;
tunica intima;
vascular smooth muscle cell
- MeSH:
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
- From:Experimental & Molecular Medicine
2007;39(1):106-113
- CountryRepublic of Korea
- Language:English
-
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.
