Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice
| Autor: | Masahiro Ikesue, Yoichiro Iwakura, Yutaka Matsui, Hideo Yagita, Junko Morimoto, Toshimitsu Uede, Hiroyuki Tsutsui, Masashi Kanayama, Koyu Ito, Daisuke Kurotaki, Daichi Ohta, Keiko Danzaki |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Apolipoprotein E
Male medicine.medical_specialty Vascular smooth muscle medicine.medical_treatment CD4 positive T cells Biology medicine.disease_cause interleukin-17A Interferon-gamma Mice Apolipoproteins E Internal medicine IL-17A medicine Animals Interferon gamma IFN-γ Aorta Mice Knockout high fat diet Interleukin-17 Interleukin Atherosclerosis Lipid Metabolism Vulnerable plaque Dietary Fats Plaque Atherosclerotic Mice Inbred C57BL Disease Models Animal interferon gamma Cytokine Endocrinology Immunoglobulin G Immunology Disease Progression Interleukin 17 Interleukin-5 Cardiology and Cardiovascular Medicine Type I collagen medicine.drug |
| Zdroj: | Arteriosclerosis, thrombosis, and vascular biology. 32(2) |
| ISSN: | 1524-4636 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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