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A functional interleukin-1 receptor antagonist polymorphism influences atherosclerosis development - The interleukin-1β: Interleukin-1 receptor antagonist balance in atherosclerosis
Örebro University, School of Health and Medical Sciences.
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2009 (English)In: Circulation Journal, ISSN 1346-9843, E-ISSN 1347-4820, Vol. 73, no 8, p. 1531-1536Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Japanese Circulation Society,Nihon Junkanki Gakkai , 2009. Vol. 73, no 8, p. 1531-1536
Keywords [en]
Atherosclerosis, Coronary artery disease, Genetic polymorphism, Immunology
National Category
Medical and Health Sciences
Research subject
Medicine
Identifiers
URN: urn:nbn:se:oru:diva-14212DOI: 10.1253/circj.CJ-08-1150ISI: 000268433600031PubMedID: 19574724Scopus ID: 2-s2.0-69049083707OAI: oai:DiVA.org:oru-14212DiVA, id: diva2:391572
Available from: 2011-01-25 Created: 2011-01-25 Last updated: 2017-12-11Bibliographically approved

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Jatta, KenSirsjö, Allan

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