Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice
Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice
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DOI：
10.1016/j.cardiores.2005.01.008
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发表时间：
2005-06-01
影响因子：
10.8
通讯作者：
Gabay, C
中科院分区：
文献类型：
--
作者：
Merhi-Soussi, F;Kwak, BR;Gabay, C
目的：目的：探讨白细胞介素（IL）-1和IL-1受体拮抗剂（IL-1 Ra）之间的平衡在动脉粥样硬化和血管炎症中的作用IL-1 Ra-/-与载脂蛋白E缺陷小鼠杂交结果：在喂食高胆固醇饮食10周的雄性中，ApoE -/-分泌型IL-1 Ra Tg（-47%）和ApoE -/-细胞内IL-1 Ra 1 Tg（-40%）的主动脉根部平均动脉粥样硬化病变面积显著降低与ApoE -/-非Tg对照相比，ApoE -/-分泌型IL-1 Ra（-53%）和ApoE -/-细胞内IL-1 Ra 1（-67%）Tg小鼠胸腹主动脉内嗜苏丹性病变的程度降低。在平行实验中，我们观察到双缺陷小鼠的早期死亡率和疾病，而ApoE -/- IL-1 Ra +/+和ApoE +/+ IL-1 Ra-/-小鼠明显健康。饮食7周后，ApoE -/- IL-1 Ra-/-小鼠表现出大量的主动脉炎症，血管结构破坏，但没有动脉粥样硬化的迹象。ApoE -/IL-1 Ra +/+小鼠有动脉粥样硬化和中度炎症反应，而ApoE +/+ IL-1 Ra-/-小鼠无血管病变。结论：IL-1/IL-1 Ra比值在ApoE-/-小鼠血管炎症和动脉粥样硬化的发病机制中起重要作用。(c)2005年欧洲心脏病学会。Elsevier B. V.出版，保留所有权利。
Objective: To examine the role of the balance between interleukin (IL)-1 and IL-1 receptor antagonist (IL-1Ra) in atherosclerosis and vascular inflammation.Methods: Transgenic (Tg) mice overexpressing either secreted IL-1Ra or intracellular IL-1Ra1 as well as IL-1Ra-deficient mice (IL-1Ra -/-) were crossed with apolipoprotein E-deficient mice (ApoE -/-).Results: In males fed a cholesterol-rich diet for 10 weeks, average atherosclerotic lesion area within aortic roots was significantly decreased in ApoE -/- secreted IL-1Ra Tg (-47%) and ApoE -/- intracellular IL-1Ra1 Tg (-40%) mice as compared to ApoE -/- non-Tg controls. The extent of sudanophilic lesions was reduced within the thoraco-abdominal aorta in ApoE -/- secreted IL-1Ra (-53%) and ApoE -/- intracellular IL-1Ra1 (-67%) Tg mice. In parallel experiments, we observed early mortality and illness among double deficient mice, whereas ApoE -/- IL-1Ra +/+ and ApoE +/+ IL-1Ra -/- mice were apparently healthy. After 7 weeks of diet, ApoE -/- IL-1Ra -/- mice exhibited massive aortic inflammation with destruction of the vascular architecture, but no signs of atherosclerosis. ApoE -/IL- 1Ra +/+ had atherosclerosis and a moderate inflammatory reaction, whereas ApoE +/+ IL- 1Ra -/- mice were free of vascular lesions. Macrophages were present in large amounts within inflammatory lesions in the adventitia of ApoE -/- IL-1Ra -/- mice.Conclusion: Our results demonstrate that the IL-1/IL-1Ra ratio plays a critical role in the pathogenic mechanisms leading to vascular inflammation and atherosclerosis in ApoE -/- mice. (c) 2005 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.