Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery.
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.
Lee
Kyeong-Min
KM
Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea.
Park
Keun-Gyu
KG
Kim
Yong-Deuk
YD
Lee
Hyo-Jung
HJ
Kim
Hyoung Tae
HT
Cho
Won-Hyun
WH
Kim
Hye-Soon
HS
Han
Seong-Wook
SW
Koh
Gou Young
GY
Park
Joong-Yeol
JY
Lee
Ki-Up
KU
Kim
Jung-Guk
JG
Lee
In-Kyu
IK
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
D000975:Antioxidants; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; D008565:Membrane Proteins; D008063:Thioctic Acid; D004247:DNA