title: Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery.
abstract: Vascular inflammation induced by the proinflammatory cytokine/NF-kappaB pathway is one of the key mechanisms in the development of neointimal hyperplasia. Accumulating evidence suggests that a recently identified chemokine, fractalkine, is involved in arterial inflammation and atherogenesis. However, no study has examined the expression of neointimal fractalkine and the effects of pharmacological agents on this process. The purposes of this study were to measure neointimal fractalkine expression in the rat carotid artery following balloon injury and to determine if alpha-lipoic acid (ALA) inhibits fractalkine expression and neointimal hyperplasia. Balloon injury of the rat carotid artery induced fractalkine expression in the medial as well as neointimal regions. ALA inhibited this expression and consequently prevented neoinitmal hyperplasia in a balloon-injured rat carotid artery. Additionally, ALA inhibited TNF-alpha-stimulated fractalkine expression in cultured vascular smooth muscle cells (VSMCs), a process which is mediated through the NF-kappaB pathway. In addition to fractalkine, ALA successfully inhibited TNF-alpha-stimulated expression of vascular cell adhesion molecule-1 and monocyte chemotactic protein-1 in cultured VSMCs. These data suggest that the cytokine-fractalkine system is involved in the pathogenesis of restenosis. The present study supports the possibility that ALA, which inhibits the NF-kappaB/fractalkine pathway, may be used to prevent neointimal hyperplasia after angioplasty or stenting.
authors.affiliation: Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
authors.forename: Kyeong-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Keun-Gyu
authors.initials: KG
authors.lastname: Park
authors.forename: Yong-Deuk
authors.initials: YD
authors.lastname: Kim
authors.forename: Hyo-Jung
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyoung Tae
authors.initials: HT
authors.lastname: Kim
authors.forename: Won-Hyun
authors.initials: WH
authors.lastname: Cho
authors.forename: Hye-Soon
authors.initials: HS
authors.lastname: Kim
authors.forename: Seong-Wook
authors.initials: SW
authors.lastname: Han
authors.forename: Gou Young
authors.initials: GY
authors.lastname: Koh
authors.forename: Joong-Yeol
authors.initials: JY
authors.lastname: Park
authors.forename: Ki-Up
authors.initials: KU
authors.lastname: Lee
authors.forename: Jung-Guk
authors.initials: JG
authors.lastname: Kim
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Lee
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015152:Blotting, Northern; D015153:Blotting, Western; D002340:Carotid Artery Diseases / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology
chemical_list: D000975:Antioxidants; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D008063:Thioctic Acid; D004247:DNA