LAUSR

An important link exists between hypertension and inflammation. Hypertensive patients present elevated circulating levels of proinflammatory cytokines, including interleukin-17A (IL-17A). This cytokine participates in host defense, autoimmune and chronic inflammatory pathologies, and cardiovascular diseases, mainly through the regulation of proinflammatory factors. Emerging evidence also suggests that IL-17A could play a role in regulating blood pressure and end-organ damage. Here, our preclinical studies in a murine model of systemic IL-17A administration show that increased levels of circulating IL-17A raised blood pressure induced inward remodeling of small mesenteric arteries (SMA) and arterial stiffness. In IL-17A-infused mice, treatment with hydralazine and hydrochlorothiazide diminished blood pressure elevation, without modifying mechanical and structural properties of small mesenteric artery, suggesting a direct vascular effect of IL-17A. The mechanisms of IL-17A seem to involve an induction of vascular smooth muscle cell hypertrophy and phenotype changes, in the absence of extracellular matrix proteins accumulation. Accordingly, treatment with an IL-17A neutralizing antibody diminished small mesenteric artery remodeling in a model of angiotensin II infusion. Moreover, in vitro studies in vascular smooth muscle cells reported here, provide further evidence of the direct effects of IL-17A on cell growth responses. Our experimental data suggest that IL-17A is a key mediator of vascular remodeling of the small arteries, which might contribute at least in part, to blood pressure elevation.