A Functional Interleukin-1 Receptor Antagonist Polymorphism Influences Atherosclerosis Development : The Interleukin-1β : Interleukin-1 Receptor Antagonist Balance in Atherosclerosis

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概要

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• Background: Interleukin (IL)-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-1Ra 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. (Circ J 2009; 73: 1531 - 1536)

• 社団法人　日本循環器学会の論文
• 2009-07-20

著者

• Eriksson Per

  Center For Molecular Medicine Department Of Medicine Karolinska University Hospital

• Sirsjo Allan

  Division Of Clinical Medicine School Of Health And Medical Sciences University Of Orebro

• OLOFSSON Peder

  Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital

• SHEIKINE Yuri

  Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital

• JATTA Ken

  Division of Clinical Medicine, School of Health and Medical Sciences, University of Orebro

• GHADERI Mehran

  Department of Radiology, Brigham and Women's Hospital, Harvard Medical School

• SAMNEGARD Ann

  Department of Clinical Sciences, Karolinska Institutet, Danderyd Hospital

• Olofsson Peder

  Center For Molecular Medicine Department Of Medicine Karolinska University Hospital

• Ghaderi Mehran

  Department Of Radiology Brigham And Women's Hospital Harvard Medical School

• Jatta Ken

  Division Of Clinical Medicine School Of Health And Medical Sciences University Of Orebro

• Samnegard Ann

  Department Of Clinical Sciences Karolinska Institutet Danderyd Hospital

• Sheikine Yuri

  Center For Molecular Medicine Department Of Medicine Karolinska University Hospital

関連論文

• A Functional Interleukin-1 Receptor Antagonist Polymorphism Influences Atherosclerosis Development : The Interleukin-1β : Interleukin-1 Receptor Antagonist Balance in Atherosclerosis

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