Interleukin-17A Deficiency Accelerates Unstable Atherosclerotic Plaque Formation in Apolipoprotein E-Deficient Mice
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概要
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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.
著者
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Matsui Yutaka
Department Of Cardiovascular Medicine Graduate School Of Medicine Hokkaido University
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Togashi Hiroko
北海道大学 医学研究科 薬理
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Tsutsui Hiroyuki
Department Of Cardiovascular Medicine
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Tsutsui Hiroyuki
Department Of Cardiovasucular Medicine Graduate School Of Medical Sciences Kyushu University
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Tsutsui Hiroyuki
Department Of Cardiovascular Medicine Hokkaido University Hospital
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Tsutsui Hiroyuki
Department Of Cardiovasucular Medicine Hokkaido University Graduate School Of Medicine
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Tsutsui Hiroyuki
Departments Of Cardiovascular Medicine Graduate School Of Medical Sciences Kyushu University:japanese Coronary Intervention Study (jcis) Group
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