Interleukin-17A induces vascular remodeling of small arteries and blood pressure elevation

Abstract

An important link exists between hypertension and inflammation. Hypertensive patientspresent elevated circulating levels of proinflammatory cytokines, including interleukin-17A(IL-17A). This cytokine participates in host defense, autoimmune and chronic inflammatorypathologies, and cardiovascular diseases, mainly through the regulation of proinflammatoryfactors. Emerging evidence also suggests that IL-17A could play a role in regulatingblood pressure and end-organ damage. Here, our preclinical studies in a murine model ofsystemic IL-17A administration showed that increased levels of circulating IL-17A raisedblood pressure induced inward remodeling of small mesenteric arteries (SMAs) and arterialstiffness. In IL-17A-infused mice, treatment with hydralazine and hydrochlorothiazidediminished blood pressure elevation, without modifying mechanical and structural propertiesof SMA, suggesting a direct vascular effect of IL-17A. The mechanisms of IL-17A seemto involve an induction of vascular smooth muscle cell (VSMC) hypertrophy and phenotypechanges, in the absence of extracellular matrix (ECM) proteins accumulation. Accordingly,treatment with an IL-17A neutralizing antibody diminished SMA remodeling in a model ofangiotensin II (Ang II) infusion. Moreover, in vitro studies in VSMCs reported here, providefurther evidence of the direct effects of IL-17A on cell growth responses. Our experimentaldata 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.