Inhibition of progression and stabilization of plaques by postnatal interferon-γ function blocking in ApoE-Knockout mice

被引:91
作者
Koga, Mitsuhisa
Kai, Hisashi
Yasukawa, Hideo
Yamamoto, Tomoka
Kawai, Yumiko
Kato, Seiya
Kusaba, Ken
Kai, Mamiko
Egashira, Kensuke
Kataoka, Yasufumi
Imaizumi, Tsutomu
机构
[1] Kurume Univ, Div Cardiovasc Med, Dept Internal Med, Kurume, Fukuoka 8300011, Japan
[2] Fukuoka Univ, Fac Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Fukuoka, Japan
[3] Kurume Univ, Cardiovasc Res Inst, Kurume, Fukuoka, Japan
[4] Kurume Univ, Dept Pathol, Kurume, Fukuoka, Japan
[5] Kyushu Univ, Grad Sch Med Sci, Dept Cardiovasc Med, Fukuoka 812, Japan
关键词
atherosclerosis; inflammation; cytokine; gene therapy;
D O I
10.1161/CIRCRESAHA.106.147256
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
A role of interferon- gamma is suggested in early development of atherosclerosis. However, the role of interferon- gamma in progression and destabilization of advanced atherosclerotic plaques remains unknown. Thus, the aim of this study was to determine whether postnatal inhibition of interferon- gamma signaling could inhibit progression of atherosclerotic plaques and stabilize the lipid- and macrophage- rich advanced plaques. Atherosclerotic plaques were induced in ApoE- knockout ( KO) mice by feeding high- fat diet from 8 weeks old ( w). Interferon- gamma function was postnatally inhibited by repeated gene transfers of a soluble mutant of interferon- gamma receptors ( sIFN gamma R), an interferon- gamma inhibitory protein, into the thigh muscle every 2 weeks. When sIFN gamma R treatment was started at 12 w ( atherosclerotic stage), sIFN gamma R not only prevented plaque progression but also stabilized advanced plaques at 16 w: sIFN gamma R decreased accumulations of the lipid and macrophages and increased fibrotic area with more smooth muscle cells. Moreover, sIFN gamma R downregulated expressions of proinflammatory cytokines, chemokines, adhesion molecules, and matrix metalloproteinases but upregulated procollagen type I. sIFN gamma R did not affect serum cholesterol levels. In conclusion, postnatal blocking of interferon- gamma function by sIFN gamma R treatment would be a new strategy to inhibit plaque progression and to stabilize advanced plaques through the antiinflammatory effects.
引用
收藏
页码:348 / 356
页数:9
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