Interleukin 17 promotes angiotensin II–induced hypertension and vascular dysfunction

MS Madhur, HE Lob, LA McCann, Y Iwakura… - …, 2010 - Am Heart Assoc
MS Madhur, HE Lob, LA McCann, Y Iwakura, Y Blinder, TJ Guzik, DG Harrison
Hypertension, 2010Am Heart Assoc
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 …
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.
Am Heart Assoc