Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction

Madhur, M.S., Lob, H.E., McCann, L.A., Iwakura, Y., Blinder, Y., Guzik, T.J. and Harrison, D.G. (2010) Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension, 55(2), pp. 500-507. (doi: 10.1161/HYPERTENSIONAHA.109.145094) (PMID:20038749) (PMCID:PMC2819301)

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Abstract

We have shown previously that T cells are required for the full development of angiotensin II–induced hypertension. However, the specific subsets of T cells that are important in this process are unknown. T helper 17 cells represent a novel subset that produces the proinflammatory cytokine interleukin 17 (IL-17). We found that angiotensin II infusion increased IL-17 production from T cells and IL-17 protein in the aortic media. To determine the effect of IL-17 on blood pressure and vascular function, we studied IL-17−/− mice. The initial hypertensive response to angiotensin II infusion was similar in IL-17−/− and C57BL/6J mice. However, hypertension was not sustained in IL-17−/− mice, reaching levels 30-mm Hg lower than in wild-type mice by 4 weeks of angiotensin II infusion. Vessels from IL-17−/− mice displayed preserved vascular function, decreased superoxide production, and reduced T-cell infiltration in response to angiotensin II. Gene array analysis of cultured human aortic smooth muscle cells revealed that IL-17, in conjunction with tumor necrosis factor-α, modulated expression of >30 genes, including a number of inflammatory cytokines/chemokines. Examination of IL-17 in diabetic humans showed that serum levels of this cytokine were significantly increased in those with hypertension compared with normotensive subjects. We conclude that IL-17 is critical for the maintenance of angiotensin II–induced hypertension and vascular dysfunction and might be a therapeutic target for this widespread disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Guzik, Professor Tomasz
Authors: Madhur, M.S., Lob, H.E., McCann, L.A., Iwakura, Y., Blinder, Y., Guzik, T.J., and Harrison, D.G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Hypertension
Publisher:American Heart Association
ISSN:0194-911X
ISSN (Online):1524-4563

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