INTERLEUKIN 17 PROMOTES ANGIOTENSIN II-INDUCED HYPERTENSION AND VASCULAR DYSFUNCTION

By Meena S. Madhur, Heinrich E. Lob, Louise A. McCann, Y. Iwakura, Yelena Blinder, T. Guzik, D. Harrison. HYPERTENSION, 2009

765 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/06a35b1a71051d9fbcef45aff973626e21f0b75c

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Citations in the corpus

Angiotensin II revisited: new roles in inflammation, immunology and aging (2010, background): “Among T cell subsets, IL-17-producing T cells are critical for the maintenance of Ang II-induced hypertension (Madhur et al, 2010).”
Inflammation, Immunity, and Hypertensive End-Organ Damage (2015, background): “We found that angiotensin II infusion increases IL-17A production from mouse T cells and that plasma levels of IL-17A are increased in humans with hypertension.(37) Importantly, mice lacking IL-17A develop blunted hypertension and do not develop endothelial dysfunction in response to angiotensin II ”