Aspirin inhibits fractalkine expression in atherosclerotic plaques and reduces atherosclerosis in ApoE gene knockout mice

Cardiovasc Drugs Ther. 2010 Feb;24(1):17-24. doi: 10.1007/s10557-009-6210-7.

Abstract

Objective: To determine the fractalkine expression in the aorta of ApoE (-/-) mice and the effect of high-dose aspirin intervention on fractalkine expression and atherosclerotic lesion formation.

Methods: Twenty-one male ApoE gene knockout mice were randomized into three groups to receive either placebo in addition to normal mice chow (n = 7), placebo in addition to a high-fat diet (n = 7), or aspirin (58 mg/kg/d) in addition to a high-fat diet (n = 7). After 12 weeks of study, the mice were euthanized and serum cholesterol, thromboxane B(2), and 6-keto-PGF(1alpha) were examined. Fractalkine and cyclooxygenase expression in aorta were measured and the atherosclerotic lesion analyzed.

Results: Pathology image analysis showed that the atherosclerotic plaque was the most extensive in the high-fat diet group while the addition of aspirin greatly reduced the severity of the plaque. Both RT-PCR analysis and immunohistochemical analysis showed that fractalkine expression was the strongest in the high-fat diet group and was significantly decreased by aspirin treatment. Serum thromboxane B(2) was lowered by aspirin while 6-keto-PGF(1alpha) and cholesterol remained unchanged.

Conclusions: The results of our study indicate that high dose aspirin can improve the atherosclerotic lesion and suppress the fractalkine expression in murine aorta.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Aorta / pathology
  • Apolipoproteins E / genetics*
  • Aspirin / pharmacology*
  • Aspirin / therapeutic use
  • Atherosclerosis / blood
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Atherosclerosis / prevention & control*
  • C-Reactive Protein / metabolism
  • Chemokine CX3CL1 / genetics
  • Chemokine CX3CL1 / metabolism*
  • Cholesterol / blood
  • Cyclooxygenase 1 / genetics
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Dietary Fats / administration & dosage
  • Gene Expression / drug effects*
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Knockout
  • Prostaglandins F / blood
  • Thromboxane B2 / blood
  • Triglycerides / blood

Substances

  • Apolipoproteins E
  • Chemokine CX3CL1
  • Cx3cl1 protein, mouse
  • Dietary Fats
  • Membrane Proteins
  • Prostaglandins F
  • Triglycerides
  • Thromboxane B2
  • C-Reactive Protein
  • Cholesterol
  • Ptgs2 protein, mouse
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Ptgs1 protein, mouse
  • Aspirin
  • prostaglandin F1