@misc{10481/87872,
year = {2020},
month = {7},
url = {https://hdl.handle.net/10481/87872},
abstract = {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.},
organization = {This work was financially supported with Grants from the Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y Competitividad (SAF2017-84894-R, SAF2014-55523-R), Junta de Andalucía (Proyecto de excelencia P12-CTS-2722 and CTS-164), Campus de Excelencia Internacional BIOTIC Granada (BS40-2015) with funds from the European Union, and the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain.},
publisher = {Journal of Hypertension.  LIPPINCOTT WILLIAMS & WILKINS.},
keywords = {endothelial dysfunction, hypertension, systemic lupus erythematosus, TLR7 activation, vascular remodelling},
title = {Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice.},
doi = {10.1097/HJH.0000000000002368},
author = {Robles-Vera, Iñaki and de la Visitación, Néstor and Toral Jiménez, Marta and Sánchez Santos, Manuel and Gómez-Guzmán, Manuel and Jiménez Moleón, Rosario and O´Valle, Francisco and Duarte Pérez, Juan Manuel and Romero Pérez, Miguel},
}