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α-Lipoic Acid Prevents Neointimal Hyperplasia Via Induction of p38 Mitogen-Activated Protein Kinase/Nur77-Mediated Apoptosis of Vascular Smooth Muscle Cells and Accelerates Postinjury Reendothelialization

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Author(s)
권택규박근규
Alternative Author(s)
Kwon, Taeg KyuPark, Keun Gyu
Publication Year
2010
Abstract
Objective—To explore whether -lipoic acid (ALA), a naturally occurring antioxidant, inhibits neointimal hyperplasia by
inducing apoptosis of vascular smooth muscle cells and to examine its potential effects on reendothelialization and
platelet aggregation.
Methods and Results—Restenosis and late stent thrombosis, caused by neointimal hyperplasia and delayed reendothelialization,
are significant clinical problems of balloon angioplasty and drug-eluting stents. ALA treatment strongly
induced apoptosis of vascular smooth muscle cells and enhanced the expression and cytoplasmic localization of Nur77,
which triggers intrinsic apoptotic events. Small interfering RNA–mediated downregulation of Nur77 diminished this
proapoptotic effect of ALA. Moreover, ALA increased p38 mitogen-activated protein kinase phosphorylation, and
inhibition of p38 mitogen-activated protein kinase completely blocked ALA-induced vascular smooth muscle cell
apoptosis and Nur77 induction and cytoplasmic localization. In balloon-injured rat carotid arteries, ALA enhanced
Nur77 expression and increased TUNEL-positive apoptotic cells in the neointima, leading to inhibition of neointimal
hyperplasia. This preventive effect of ALA was significantly reduced by infection of an adenovirus encoding Nur77
small hairpin (sh)RNA. Furthermore, ALA reduced basal apoptosis of human aortic endothelial cells and accelerated
reendothelialization after balloon injury. ALA also suppressed arachidonic acid–induced platelet aggregation.
Conclusion—ALA could be a promising therapeutic agent to prevent restenosis and late stent thrombosis after angioplasty
and drug-eluting stent implantation. (Arterioscler Thromb Vasc Biol. 2010;30:2164-2172.)
Key Words: apoptosis -lipoic acid Nur77 VSMC neointimal hyperplasia
Department
Dept. of Immunology (면역학)
Dept. of Internal Medicine (내과학)
Publisher
School of Medicine
Citation
Arteriosclerosis, Thrombosis, and Vascular Biology, Vol.30(11) : 2164-2172, 2010
Type
Article
ISSN
1079-5642
DOI
10.1161/ATVBAHA.110.212308
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/35102
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