Alpha-lipoic acid inhibits fractalkine expression and prevents neointimal hyperplasia after balloon injury in rat carotid artery

Atherosclerosis. 2006 Nov;189(1):106-14. doi: 10.1016/j.atherosclerosis.2005.12.003. Epub 2006 Jan 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angioplasty, Balloon / adverse effects
  • Animals
  • Antioxidants / pharmacology*
  • Blotting, Northern
  • Blotting, Western
  • Carotid Artery Diseases / metabolism
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / prevention & control*
  • Cells, Cultured
  • Chemokine CX3CL1
  • Chemokines, CX3C* / antagonists & inhibitors
  • Chemokines, CX3C* / biosynthesis
  • Chemokines, CX3C* / genetics
  • DNA / genetics*
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression*
  • Hyperplasia / prevention & control
  • Male
  • Membrane Proteins* / antagonists & inhibitors
  • Membrane Proteins* / biosynthesis
  • Membrane Proteins* / genetics
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Thioctic Acid / pharmacology*
  • Tunica Intima / drug effects
  • Tunica Intima / pathology

Substances

  • Antioxidants
  • Chemokine CX3CL1
  • Chemokines, CX3C
  • Cx3cl1 protein, rat
  • Membrane Proteins
  • Thioctic Acid
  • DNA