期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 32, 期 2, 页码 273-U255出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.111.229997
关键词
atherosclerosis; CD4 positive T cells; high fat diet; interferon gamma; interleukin-17A
资金
- Ministry of Education, Culture, Science, Sports, and Technology of Japan [21390113(B)]
- Uehara Memorial Foundation
- Grants-in-Aid for Scientific Research [21390113] Funding Source: KAKEN
Objective-Interleukin(IL)-17A, an inflammatory cytokine, has been implicated in atherosclerosis, in which inflammatory cells within atherosclerotic plaques express IL-17A. However, its role in the development of atheroscelrosis remains to be controversial. Methods and Results-To directly examine the role of IL-17A in atherosclerosis, we generated apolipoprotein E (ApoE)/IL-17A double-deficient (ApoE(-/-)IL-17A(-/-)) mice. Mice were fed with high-fat diet (HFD) for either 8 or 16 weeks, both starting at ages of 6 to 8 weeks. We found that splenic CD4(+) T-cells produced high amounts of IL-17A in ApoE(-/-) mice after HFD feeding for 8 weeks. Atherosclerosis was significantly accelerated in HFD-fed ApoE(-/-)IL-17A(-/-) mice compared with ApoE(-/-) mice. Splenic CD4(+) T-cells of ApoE(-/-) IL-17A(-/-) mice after HFD feeding for 8 weeks, but not for 16 weeks, exhibited increased interferon gamma and decreased IL-5 production. Importantly, formation of vulnerable plaque as evidenced by reduced numbers of vascular smooth muscle cells and reduced type I collagen deposition in the plaque was detected in ApoE(-/-)IL-17A(-/-) mice after HFD feeding for 8 weeks. Conclusion-These results suggest that IL-17A regulates the early phase of atherosclerosis development after HFD feeding and plaque stability, at least partly if not all by modulating interferon gamma and IL-5 production from CD4(+) T-cells. (Arterioscler Thromb Vasc Biol. 2012;32:273-280.)
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