A novel inhibitory effect of naloxone on macrophage activation and atherosclerosis formation in mice

J Am Coll Cardiol. 2006 Nov 7;48(9):1871-9. doi: 10.1016/j.jacc.2006.07.036. Epub 2006 Oct 17.

Abstract

Objectives: We investigated whether naloxone could reduce macrophage activation and influence atherosclerotic lesion formation in mice.

Background: Macrophages play an important role in the inflammatory process in atherosclerosis. Naloxone could inhibit activation of microglia, the resident macrophage in the nervous system.

Methods: The anti-inflammatory effect of naloxone was evaluated by stimulating the macrophage cell culture and FVB mice with lipopolysaccharide or oxidized low-density lipoprotein with and without naloxone pretreatment. Apolipoprotein-E (apoE)-deficient mice received naloxone injection for 10 weeks, and the severity of aortic atherosclerosis was measured. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice then received naloxone injection for 4 weeks after ligation, and the severity of neointima formation was evaluated.

Results: Naloxone pretreatment significantly suppressed the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-6, monocyte chemoattractant protein-1, and superoxide in macrophages after stimulation. In FVB mice, naloxone reduced the TNF-alpha level in circulation, inflammatory cell infiltration in lungs, and superoxide production in aorta. Naloxone injection significantly decreased the severity of aortic atherosclerosis in the apoE-deficient mice and carotid neointima formation in the C57BL/6 mice after ligation.

Conclusions: Naloxone, with its novel anti-inflammatory effect, significantly reduces atherosclerosis and neointima formation in mice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Atherosclerosis / drug therapy
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • Cell Line, Tumor
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Humans
  • Macrophage Activation / drug effects*
  • Macrophage Activation / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Naloxone / pharmacology*
  • Naloxone / therapeutic use

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Naloxone