Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice
Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice
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DOI：
10.1161/01.atv.0000127025.48140.a3
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发表时间：
2004-06-01
影响因子：
8.7
通讯作者：
Ohsuzu, F
中科院分区：
文献类型：
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作者：
Isoda, K;Sawada, S;Ohsuzu, F
目的白介素1(IL-1)在动脉粥样硬化中起重要作用。IL-1受体拮抗剂(IL-1ra)是IL-1的内源性抑制物。然而，IL-1ra在动脉粥样硬化形成中的作用还不是很清楚。方法和结果-缺乏IL-1ra(IL-1ra-/-)的小鼠与载脂蛋白E缺陷(E-/-)小鼠杂交，分析正常饮食16周和32周后动脉粥样硬化病变的形成。本研究重点比较了IL-1Ra+/+/apoE-/-小鼠(n=12)和IL-1Ra(+/-)/apoE-/-小鼠(n=12)的动脉粥样硬化病变，因为IL-1Ra-/-/apoE-/-小鼠的表型明显比其他小鼠瘦。有趣的是，16周龄IL-1Ra+/-/apoE-/-小鼠的动脉粥样硬化病变面积显著大于IL-1Ra+/+/apoE-/-小鼠(P<；0.05)。在32周时，这些小鼠之间的病变大小差异没有达到统计学意义。然而，免疫染色显示IL-1ra+/-/apoE-/-小鼠的MOMA-2染色损伤面积增加了86%(P<；0.0001)。此外，与IL-1ra+/+/apoE-/-小鼠相比，这些斑块中α-肌动蛋白的染色显著减少(-15%)。结论：这些结果提示IL-1ra在动脉粥样硬化形成早期抑制病变发展中起重要作用，并进一步表明其在斑块成分调节中的作用。
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.