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Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice
Open accessAbstract
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.
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Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J. G., Rubin, E. M., & Breslow, J. L. (1992) · Cell · doi:10.1016/0092-8674(92)90362-g · Cited by 2,263
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Cytokines in atherosclerosis: Key players in all stages of disease and promising therapeutic targets
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Self-citationKoenig, W. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.07.113 · Cited by 315
Metadata
- Authors
- MERHISOUSSI, F., KWAK, B., MAGNE, D., CHADJICHRISTOS, C., BERTI, M., PELLI, G., JAMES, R., MACH, F., & GABAY, C.
- Venue
- Cardiovascular Research
- Publisher
- Oxford University Press (OUP)
- Published
- 2005-06-01
- Volume
- 66
- Issue
- 3
- Pages
- 583-593
- ISSN
- 0008-6363 (ISSN-L)
- OpenAlex
- W2029607791
- Cited by
- 200
- References
- 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- bronze
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- MERHISOUSSI, F., KWAK, B., MAGNE, D., CHADJICHRISTOS, C., BERTI, M., PELLI, G., JAMES, R., MACH, F., & GABAY, C. (2005). Interleukin-1 plays a major role in vascular inflammation and atherosclerosis in male apolipoprotein E-knockout mice. Cardiovascular Research. https://doi.org/10.1016/j.cardiores.2005.01.008
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