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

Madhur MS, Funt SA, Li L, Vinh A, Chen W, Lob HE, Iwakura Y, Blinder Y, Rahman A, Quyyumi AA, Harrison DG
Arterioscler Thromb Vasc Biol. 2011 31 (7): 1565-72

PMID: 21474820 · PMCID: PMC3117048 · DOI:10.1161/ATVBAHA.111.227629

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.

CONCLUSIONS - 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.

MeSH Terms (30)

Aged Angiotensin II Animals Antibodies, Neutralizing Aorta Aortic Diseases Apolipoproteins E Atherosclerosis Carotid Arteries Carotid Artery Diseases Cells, Cultured Dendritic Cells Dietary Fats Disease Models, Animal Female Humans Inflammation Interferon-gamma Interleukin-17 Ligation Lymphocytes Male Mice Mice, Inbred C57BL Mice, Knockout Middle Aged Nitric Oxide Spleen Superoxides Time Factors

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