Lack of Interleukin1 Receptor Antagonist Modulates Plaque Composition in Apolipoprotein E-Deficient Mice
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/ (n12) and IL-1Ra//apoE/ mice (n12), 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 (P0.05). At 32 weeks, the differences of lesion size between these mice failed to achieve statistical significance. However, immunostaining demonstrated an 86% (P0.0001) 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 (P0.05). 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. (Arterioscler Thromb Vasc Biol. 2004;24:1068-1073.)
Published in 2010.