Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction.
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.
Madhur
Meena S
MS
Division of Cardiology, Emory University, Atlanta, GA 30322, USA.
Lob
Heinrich E
HE
McCann
Louise A
LA
Iwakura
Yoichiro
Y
Blinder
Yelena
Y
Guzik
Tomasz J
TJ
Harrison
David G
DG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000503:physiopathology; D002478:Cells, Cultured; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology; D020381:Interleukin-17 / Q000097:blood*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D013601:T-Lymphocytes / Q000378:metabolism; D014652:Vascular Diseases / Q000139:chemically induced / Q000378:metabolism*
D020381:Interleukin-17; D000804:Angiotensin II