Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. Robles-Vera, Iñaki de la Visitación, Néstor Toral Jiménez, Marta Sánchez Santos, Manuel Gómez-Guzmán, Manuel Jiménez Moleón, Rosario O´Valle, Francisco Duarte Pérez, Juan Manuel Romero Pérez, Miguel endothelial dysfunction, hypertension, systemic lupus erythematosus, TLR7 activation, vascular remodelling Objective: To investigate whether toll-like receptor 7 (TLR7) activation induces an increase in blood pressure and vascular damage in wild-type mice treated with the TLR7 agonist imiquimod (IMQ). Methods: Female BALB/c mice (7-9 week old) were randomly assigned to two experimental groups: an untreated control group and a group treated topically with IMQ (IMQ-treated) for 4 or 8 weeks. A group of IMQ-treated mice that take a combination of the antioxidants tempol and apocynin, and another treated IL-17-neutralizing antibody were also performed. Results: TLR7 activation gradually increased blood pressure, associated with elevated plasma levels of anti-dsDNA autoantibodies, splenomegaly, hepatomegaly, and severe expansion of splenic immune cells with an imbalance between proinflammatory T cells and regulatory T cells. TLR7 activation induced a marked vascular remodeling in mesenteric arteries characterized by an increased media--lumen ratio (≈40%), and an impaired endothelium-dependent vasorelaxation in aortas from wild-type mice after 8 weeks of treatment. In addition, an increased ROS production, as a result of the upregulation of NADPH oxidase subunits, and an enhanced vascular inflammation were found in aortas from IMQ-treated mice. These functional and structural vascular alterations induced by IMQ were improved by antioxidant treatment. Anti-IL-17 treatment reduced blood pressure and improved endothelial dysfunction in IMQ-treated mice. Conclusion: Our results demonstrate that TLR7 activation induces the development of hypertension and vascular damage in BALB/c mice, and further underscore the increased vascular inflammation and oxidative stress, mediated in part by IL-17, as key factors contributing to cardiovascular complications in this TLR7-driven lupus autoimmunity model. 2024-02-01T08:39:56Z 2024-02-01T08:39:56Z 2020-07 journal article Robles-Vera I, Visitación N, Toral M, Sánchez M, Gómez-Guzmán M, O'valle F, Jiménez R, Duarte J, Romero M. Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. J Hypertens. 2020 Jul;38(7):1322-1335. doi: 10.1097/HJH.0000000000002368. PMID: 32004206. https://hdl.handle.net/10481/87872 10.1097/HJH.0000000000002368 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Journal of Hypertension. LIPPINCOTT WILLIAMS & WILKINS.