Interleukin-17A induces vascular remodeling of small arteries and blood pressure elevation. Issue 5 (9th March 2020)

• Record Type: Journal Article
• Authors: Orejudo, Macarena; García-Redondo, Ana B.; Rodrigues-Diez, Raúl R.; Rodrigues-Díez, Raquel; Santos-Sanchez, Laura; Tejera-Muñoz, Antonio; Egido, Jesús; Selgas, Rafael; Salaices, Mercedes; Briones, Ana M.; Ruiz-Ortega, Marta
• Is Part Of: Clinical science. Volume 134:Issue 5(2020)
• Page Start: 513
• Page End: 527
• Publication Date: 2020-03-09
• Subjects: hypertension -- hypertrophy -- Interleukin-17 -- remodelling -- stiffness; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20190682
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: 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 showed that increased levels of circulating IL-17A raised blood pressure induced inward remodeling of small mesenteric arteries (SMAs) and arterial stiffness. In IL-17A-infused mice, treatment with hydralazine and hydrochlorothiazide diminished blood pressure elevation, without modifying mechanical and structural properties of SMA, suggesting a direct vascular effect of IL-17A. The mechanisms of IL-17A seem to involve an induction of vascular smooth muscle cell (VSMC) hypertrophy and phenotype changes, in the absence of extracellular matrix (ECM) proteins accumulation. Accordingly, treatment with an IL-17A neutralizing antibody diminished SMA remodeling in a model of angiotensin II (Ang II) infusion. Moreover, in vitro studies in VSMCs 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.