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Circulation. 2002;106:1282-1287
Published online before print August 12, 2002, doi: 10.1161/01.CIR.0000027816.54430.96
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(Circulation. 2002;106:1282.)
© 2002 American Heart Association, Inc.


Basic Science Reports

Effect of Low-Dose Aspirin on Vascular Inflammation, Plaque Stability, and Atherogenesis in Low-Density Lipoprotein Receptor–Deficient Mice

Tillmann Cyrus, MD; Syuan Sung, BSc; Lei Zhao, MD; Colin D. Funk, PhD; Syun Tang, MD; Domenico Praticò, MD

From the Center for Experimental Therapeutics and Department of Pharmacology, University of Pennsylvania, School of Medicine, Philadelphia.

Correspondence to Domenico Praticò, MD, Center for Experimental Therapeutics, Room 812, Biomedical Research Bldg 2/3, University of Pennsylvania, Philadelphia, PA 19104. E-mail domenico{at}spirit.gcrc.upenn.edu

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 {kappa}B 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.


Key Words: atherosclerosis • aspirin • inflammation • plaque




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