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Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice

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Title: Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice
Authors: Danzaki, Keiko Browse this author
Matsui, Yutaka Browse this author →KAKEN DB
Ikesue, Masahiro Browse this author
Ohta, Daichi Browse this author
Ito, Koyu Browse this author
Kanayama, Masashi Browse this author
Kurotaki, Daisuke Browse this author
Morimoto, Junko Browse this author →KAKEN DB
Iwakura, Yoichiro Browse this author
Yagita, Hideo Browse this author
Tsutsui, Hiroyuki Browse this author →KAKEN DB
Uede, Toshimitsu Browse this author →KAKEN DB
Keywords: atherosclerosis
CD4 positive T cells
high fat diet
interferon gamma
Issue Date: Feb-2012
Publisher: American Heart Association
Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology
Volume: 32
Issue: 2
Start Page: 273
End Page: 280
Publisher DOI: 10.1161/ATVBAHA.111.229997
PMID: 22116098
Abstract: Objective: Interleukin-17A (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 6-8 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 IFN-γ 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. Conclusions: 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 IFN-γ and IL-5 production from CD4+ T-cells.
Type: article (author version)
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 檀崎 敬子

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