alexa Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice.


Translational Medicine

Author(s): Isoda K, Sawada S, Ishigami N, Matsuki T, Miyazaki K,

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Abstract 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, alpha-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. This article was published in Arterioscler Thromb Vasc Biol and referenced in Translational Medicine

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