Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein e-deficient mice

Keiko Danzaki, Yutaka Matsui, Masahiro Ikesue, Daichi Ohta, Koyu Ito, Masashi Kanayama, Daisuke Kurotaki, Junko Morimoto, Yoichiro Iwakura, Hideo Yagita, Hiroyuki Tsutsui, Toshimitsu Uede

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)273-280
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number2
DOIs
Publication statusPublished - Feb 1 2012

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Interleukin-17
Apolipoproteins
Atherosclerotic Plaques
High Fat Diet
Apolipoproteins E
Atherosclerosis
Interleukin-5
T-Lymphocytes
Interferon-gamma
Collagen Type I
Vascular Smooth Muscle
Smooth Muscle Myocytes
Cytokines

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein e-deficient mice. / Danzaki, Keiko; Matsui, Yutaka; Ikesue, Masahiro; Ohta, Daichi; Ito, Koyu; Kanayama, Masashi; Kurotaki, Daisuke; Morimoto, Junko; Iwakura, Yoichiro; Yagita, Hideo; Tsutsui, Hiroyuki; Uede, Toshimitsu.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 32, No. 2, 01.02.2012, p. 273-280.

Research output: Contribution to journalArticle

Danzaki, K, Matsui, Y, Ikesue, M, Ohta, D, Ito, K, Kanayama, M, Kurotaki, D, Morimoto, J, Iwakura, Y, Yagita, H, Tsutsui, H & Uede, T 2012, 'Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein e-deficient mice', Arteriosclerosis, thrombosis, and vascular biology, vol. 32, no. 2, pp. 273-280. https://doi.org/10.1161/ATVBAHA.111.229997
Danzaki, Keiko ; Matsui, Yutaka ; Ikesue, Masahiro ; Ohta, Daichi ; Ito, Koyu ; Kanayama, Masashi ; Kurotaki, Daisuke ; Morimoto, Junko ; Iwakura, Yoichiro ; Yagita, Hideo ; Tsutsui, Hiroyuki ; Uede, Toshimitsu. / Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein e-deficient mice. In: Arteriosclerosis, thrombosis, and vascular biology. 2012 ; Vol. 32, No. 2. pp. 273-280.
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