Aspirin Inhibits Fractalkine Expression in Atherosclerotic Plaques and Reduces Atherosclerosis in ApoE Gene Knockout Mice

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 B₂, and $6 - {\text{keto}} - {\text{PG}}{{\text{F}}_{1\alpha }}$ 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 B₂ was lowered by aspirin while $6 - {\text{keto}} - {\text{PG}}{{\text{F}}_{1\alpha }}$ 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.