Effect of low-dose aspirin on vascular inflammation, plaque stability, and atherogenesis in low-density lipoprotein receptor-deficient mice

Circulation. 2002 Sep 3;106(10):1282-7. doi: 10.1161/01.cir.0000027816.54430.96.

Abstract

Background: Atherosclerosis is a complex vascular inflammatory disease. Low-dose aspirin is a mainstay in the prevention of vascular complications of atherosclerosis. We wished to determine the effect of low-dose aspirin on vascular inflammation, plaque composition, and atherogenesis in LDL receptor-deficient mice fed a high fat diet.

Methods and results: In LDL receptor-deficient mice fed a high fat diet compared with control mice, low-dose aspirin induced a significant decrease in circulating levels and vascular formation of soluble intercellular molecule-1, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin-12p 40, without affecting lipid levels. This was associated with significant reduction of the nuclear factor kappaB activity in the aorta. Low-dose aspirin also significantly reduced the extent of atherosclerosis. Finally, aortic vascular lesions of the aspirin-treated animals showed 57% reduction (P<0.05) in the amount of macrophage cells, 77% increase in smooth muscle cells (P<0.05), and 23% increase in collagen (P<0.05).

Conclusions: Our results suggest that in murine atherosclerosis, low-dose aspirin suppresses vascular inflammation and increases the stability of atherosclerotic plaques, both of which, together with its antiplatelet activity, contribute to its antiatherogenic effect. We conclude that low-dose aspirin might be rationally evaluated in the progression and evolution of human atherosclerotic plaque.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology
  • Arteriosclerosis / drug therapy*
  • Arteriosclerosis / metabolism
  • Arteriosclerosis / pathology
  • Aspirin / administration & dosage
  • Aspirin / therapeutic use*
  • Culture Techniques
  • Cytokines / biosynthesis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Receptors, LDL / genetics*
  • Vasculitis / drug therapy*
  • Vasculitis / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • NF-kappa B
  • Receptors, LDL
  • Aspirin