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

被引:133
作者
Isoda, K
Sawada, S
Ishigami, N
Matsuki, T
Miyazaki, K
Kusuhara, M
Iwakura, Y
Ohsuzu, F
机构
[1] Natl Def Med Coll, Tokorozawa, Saitama 3598513, Japan
[2] Univ Tokyo, Inst Med Sci, Ctr Med Expt, Tokyo, Japan
关键词
atherosclerosis; immune system; inflammation; interleukins; macrophage;
D O I
10.1161/01.ATV.0000127025.48140.a3
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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-1Ra-/-) 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, alpha-actin staining in these lesions was significantly decreased (-15%) compared with those in IL-1Ra+/+/apoE-/- mice (P < 0.05). 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.
引用
收藏
页码:1068 / 1073
页数:6
相关论文
共 35 条
[31]   Involvement of chemokine receptor 2 and its ligand, monocyte chemoattractant protein-1, in the development of atherosclerosis: lessons from knockout mice [J].
Peters, W ;
Charo, IF .
CURRENT OPINION IN LIPIDOLOGY, 2001, 12 (02) :175-180
[32]   Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice [J].
Ramos, CL ;
Huo, YQ ;
Jung, US ;
Ghosh, S ;
Manka, DR ;
Sarembock, IJ ;
Ley, K .
CIRCULATION RESEARCH, 1999, 84 (11) :1237-1244
[33]   Interleukin-1β induces tissue- and cell type-specific expression of adhesion molecules in vivo [J].
Tamaru, M ;
Tomura, K ;
Sakamoto, S ;
Tezuka, K ;
Tamatani, T ;
Narumi, S .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1998, 18 (08) :1292-1303
[34]  
TANGIRALA RK, 1995, J LIPID RES, V36, P2320
[35]   Hypercholesterolemia is associated with a T helper (Th) 1 Th2 switch of the autoimmune response in atherosclerotic apo E knockout mice [J].
Zhou, XH ;
Paulsson, G ;
Stemme, S ;
Hansson, GK .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (08) :1717-1725