Interleukin-17A deficiency accelerates unstable atherosclerotic plaque formation in apolipoprotein E-deficient mice.
Arterioscler Thromb Vasc Biol
; 32(2): 273-80, 2012 Feb.
Article
em En
| MEDLINE
| ID: mdl-22116098
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 ANDRESULTS:
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.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 interferon gamma and IL-5 production from CD4(+) T-cells.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Apolipoproteínas E
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Progressão da Doença
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Interleucina-17
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Aterosclerose
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Placa Aterosclerótica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article