Open AccessInterleukin-17A induces vascular remodeling of small arteries and blood pressure elevation
Author(s) -
Macarena Orejudo,
Ana B. García-Redondo,
Raúl R. Rodrigues-Díez,
Raquel RodriguesDíez,
Laura Santos-Sánchez,
Antonio TejeraMuñoz,
Jesús Egido,
Rafael Selgas,
Mercedes Salaíces,
Ana M. Briones,
Marta Ruíz-Ortega
Publication year - 2020
Publication title -
clinical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.91
H-Index - 138
eISSN - 1470-8736
pISSN - 0143-5221
DOI - 10.1042/cs20190682
Subject(s) - proinflammatory cytokine , vascular smooth muscle , medicine , angiotensin ii , blood pressure , hydralazine , endocrinology , inflammation , extracellular matrix , muscle hypertrophy , immunology , biology , microbiology and biotechnology , smooth muscle
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.