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A functional interleukin-1 receptor antagonist polymorphism influences atherosclerosis development - The interleukin-1β : Interleukin-1 receptor antagonist balance in atherosclerosis
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- Olofsson, P. S. (author)
- Karolinska Institutet
- Sheikine, Y. (author)
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- Jatta, Ken (author)
- Örebro universitet,Hälsoakademin
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- Japanese Circulation Society,Nihon Junkanki Gakkai, 2009
- 2009
- English.
- In: Circulation Journal. - : Japanese Circulation Society,Nihon Junkanki Gakkai. - 1346-9843 .- 1347-4820. ; 73:8, s. 1531-1536
- Journal article (peer-reviewed)
Abstract
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- Background: Interleukin (JL)-β plays a central role in inflammation and atherosclerosis, but levels of IL-1β, its natural antagonist, IL-1Ra, and their balance in human atherosclerotic lesions, are unknown. Knowledge of protein levels in atherosclerosis and the influence of a functional IL-1Rα polymorphism would increase the understanding of atherosclerosis pathogenesis.Methods and Results: Fresh and endotoxin-stimulated explanted human atherosclerotic and normal arteries were analyzed for IL-1β, IL-1Ra and IL-1 receptor 1 (IL-1R1) using TaqMan PCR and enzyme-linked immunosorbent assay. Two hundred forty-three survivors of a first myocardial infarction were genotyped for a polymorphism in IL-1Ra and their coronary atherosclerosis analyzed by using coronary angiography. Levels of IL-1β, IL-1Ra and IL-1R1 mRNA were significantly increased in atherosclerotic arteries compared with normal arteries. Endotoxin stimulation increased IL-1β levels more than IL-1Ra levels (ie, promoted a pro-inflammatory state). A polymorphism in IL-1Ra known to increase levels of IL-1Ra was associated with decreased mean coronary artery plaque area.Conclusions: Activation of innate immunity changed the balance between IL-1β and IL-1Ra in atherosclerotic arteries towards a more pro-inflammatory state. In line with this, the presence of an IL-1Ra intron 2 polymorphism known to increase IL-1Ra levels, and possibly the IL-1Ra:IL-1β ratio, was associated with reduced coronary atherosclerosis.
Keyword
- Atherosclerosis
- Coronary artery disease
- Genetic polymorphism
- Immunology
- MEDICINE
- MEDICIN
- Medicine
- Medicin
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Olofsson, P. S.
- Sheikine, Y.
- Jatta, Ken
- Ghaderi, M.
- Samnegård, A.
- Eriksson, P.
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- Sirsjö, Allan
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- Örebro University
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