Lack of interleukin-1 receptor antagonist modulates plaque composition in apolipoprotein E-deficient mice

Kikuo Isoda, Shojiro Sawada, Norio Ishigami, Taizo Matsuki, Koji Miyazaki, Masatoshi Kusuhara, Yoichiro Iwakura, Fumitaka Ohsuzu

Research output: Contribution to journalArticle

109 Citations (Scopus)

Abstract

Objective-Interleukin (IL)-1 plays an important role in atherosclerosis. IL-1 receptor antagonist (IL-1Ra) is an endogenous inhibitor of IL-1. However, the role of IL-1Ra in the development of atherosclerosis is poorly understood. Methods and Results-Mice that lacked IL-1Ra (IL-/-) were crossed with apolipoprotein E-deficient (E-/-) mice and formation of atherosclerotic lesions was analyzed after 16 weeks or 32 weeks consumption of a normal chow diet. This study focused on the comparison of atherosclerotic lesion between IL-1Ra+/+/apoE-/- (n=12) and IL-1Ra+/-/apoE-/- mice (n=12), because of the significantly leaner phenotype in IL-1Ra-/-/apoE-/- mice compared with the others. Interestingly, atherosclerotic lesion size in IL-1Ra+/-/apoE-/- mice at age 16 weeks was significantly increased (30%) compared with IL-1Ra+/+/apoE-/- mice (P<0.05). At 32 weeks, the differences of lesion size between these mice failed to achieve statistical significance. However, immunostaining demonstrated an 86% (P<0.0001) increase in the MOMA-2-stained lesion area of IL-1Ra+/-/apoE-/- mice. In addition, α-actin staining in these lesions was significantly decreased (-15%) compared with those in IL-1Ra+/+/apoE-/- mice (Pα0.05). Conclusions-These results suggest an important role of IL-1Ra in the suppression of lesion development during early atherogenesis and furthermore indicate its role in the modulation of plaque composition.

Original languageEnglish
Pages (from-to)1068-1073
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number6
DOIs
Publication statusPublished - 2004 Jun

Keywords

  • Atherosclerosis
  • Immune system
  • Inflammation
  • Interleukins
  • Macrophage

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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