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 journalArticlepeer-review

114 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 2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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