Published online before print April 1, 2004, doi: 10.1161/01.ATV.0000127025.48140.a3
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© 2004 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Lack of Interleukin-1 Receptor Antagonist Modulates Plaque Composition in Apolipoprotein E–Deficient Mice
From Internal Medicine I (K.I., S.S., N.I., K.M., M.K., F.O.), National Defense Medical College, Tokorozawa, Japan; and the Center for Experimental Medicine (T.M., Y.I.), Institute of Medical Science, University of Tokyo, Japan.
Correspondence to Dr Kikuo Isoda, Internal Medicine I, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama, 359-8513, Japan. E-mail isoda{at}me.ndmc.ac.jp
Objective— Interleukin (IL)-1 plays an important role in atherosclerosis. IL-1 receptor antagonist (IL-1Ra) is an endogenous inhibitor of IL-1. However, the role of IL-1Ra in the development of atherosclerosis is poorly understood.
Methods and Results— Mice that lacked IL-1Ra (IL-1Ra–/–) were crossed with apolipoprotein E-deficient (E–/–) mice and formation of atherosclerotic lesions was analyzed after 16 weeks or 32 weeks consumption of a normal chow diet. This study focused on the comparison of atherosclerotic lesion between IL-1Ra+/+/apoE–/– (n=12) and IL-1Ra+/–/apoE–/– mice (n=12), because of the significantly leaner phenotype in IL-1Ra–/–/apoE–/– mice compared with the others. Interestingly, atherosclerotic lesion size in IL-1Ra+/–/apoE–/– mice at age 16 weeks was significantly increased (30%) compared with IL-1Ra+/+/apoE–/– mice (P<0.05). At 32 weeks, the differences of lesion size between these mice failed to achieve statistical significance. However, immunostaining demonstrated an 86% (P<0.0001) increase in the MOMA-2–stained lesion area of IL-1Ra+/–/apoE–/– mice. In addition, 
-actin staining in these lesions was significantly decreased (–15%) compared with those in IL-1Ra+/+/apoE–/– mice (P<0.05).
Conclusions— These results suggest an important role of IL-1Ra in the suppression of lesion development during early atherogenesis and furthermore indicate its role in the modulation of plaque composition.
We investigated the contribution of interleukin-1 receptor antagonist (IL-1Ra) to atherosclerosis by comparing apolipoprotein E single knockout (IL-1Ra+/+/apoE–/–) with IL-1Ra+/–/apoE–/– mice. Immunostaining at age 32 weeks old showed an 86% increase in the MOMA-2–stained lesion area of IL-1Ra+/–/apoE–/–, whereas -actin staining was significantly diminished compared with IL-1Ra+/+/apoE–/– mice.
Key Words: atherosclerosis • immune system • inflammation • interleukins • macrophage
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