Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice
| Autor: | Faten Merhi-Soussi, Richard W. James, Christos Chadjichristos, David Magne, Marina Berti, François Mach, Graziano Pelli, Cem Gabay, Brenda R. Kwak |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Apolipoprotein E medicine.medical_specialty Pathology Apolipoprotein B Endothelium Physiology Aorta Thoracic Mice Transgenic Inflammation Mice chemistry.chemical_compound Apolipoproteins E Physiology (medical) Internal medicine medicine Animals Receptor Mice Knockout Serum Amyloid A Protein biology Cholesterol Receptors Interleukin-1 Interleukin Atherosclerosis Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry Mice Inbred DBA biology.protein Diet Atherogenic lipids (amino acids peptides and proteins) Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine Interleukin-1 Blood vessel |
| Zdroj: | Cardiovascular Research. 66:583-593 |
| ISSN: | 0008-6363 |
| DOI: | 10.1016/j.cardiores.2005.01.008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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