Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.

Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ, Harrison DG
Hypertension. 2010 55 (2): 500-7

PMID: 20038749 · PMCID: PMC2819301 · DOI:10.1161/HYPERTENSIONAHA.109.145094

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-alpha, 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.

MeSH Terms (20)

Angiotensin II Animals Atherosclerosis Cells, Cultured Cohort Studies Diabetes Mellitus, Type 2 Disease Models, Animal Female Humans Hypertension Interleukin-17 Lymphocyte Activation Male Mice Mice, Inbred C57BL Probability Random Allocation Reference Values T-Lymphocytes Vascular Diseases

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