Role of interleukin 17 in inflammation, atherosclerosis, and vascular function in apolipoprotein e-deficient mice

Meena S. Madhur, Samuel A. Funt, Li Li, Antony Vinh, Wei Chen, Heinrich E. Lob, Yoichiro Iwakura, Yelena Blinder, Ayaz Rahman, Arshed A. Quyyumi, David G. Harrison

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135 Citations (Scopus)

Abstract

Objective-: Interleukin 17A (IL17A) is involved in many inflammatory processes, but its role in atherosclerosis remains controversial. We examined the role of IL17A in mouse and human atherosclerosis. Methods and Results-: Atherosclerosis was induced in apolipoprotein E (ApoE)-/- and IL17A/ApoE-/- mice using high-fat feeding, angiotensin II infusion, or partial carotid ligation. In ApoE-/- mice, 3 months of high-fat diet induced interferon-γ production by splenic lymphocytes, and this was abrogated in IL17A/ApoE-/- mice. IL17A/ApoE-/- mice had reduced aortic superoxide production, increased aortic nitric oxide levels, decreased aortic leukocyte and dendritic cell infiltration, and reduced weight gain after a high-fat diet compared with ApoE-/- mice. Despite these favorable effects, IL17A deficiency did not affect aortic plaque burden after a high-fat diet or angiotensin II infusion. In a partial carotid ligation model, IL17A deficiency did not affect percentage of stenosis but reduced outward remodeling. In this model, neutralization of the related isoform, IL17F, in IL17A/ApoE-/- mice did not alter atherosclerosis. Finally, there was no correlation between IL17A levels and carotid intima-media thickness in humans. Conclusion-: IL17 contributes to vascular and systemic inflammation in experimental atherosclerosis but does not alter plaque burden. The changes in plaque composition caused by IL17 might modulate plaque stability. 

Original languageEnglish
Pages (from-to)1565-1572
Number of pages8
JournalArteriosclerosis, Thrombosis and Vascular Biology
Volume31
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • atherosclerosis
  • cytokines
  • nitric oxide
  • superoxide
  • vascular biology

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