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Article Dans Une Revue Cardiovascular Research Année : 2005

Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice

Résumé

Abstract 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.

Dates et versions

hal-03838505 , version 1 (03-11-2022)

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F Merhisoussi, B Kwak, D Magne, Christos Chadjichristos, M Berti, et al.. Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice. Cardiovascular Research, 2005, 66 (3), pp.583-593. ⟨10.1016/j.cardiores.2005.01.008⟩. ⟨hal-03838505⟩
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