2026-07-21T15:39:27Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/103062024-09-27T08:41:21Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud
author
Robles-Vera, Iñaki
author
Visitación, Néstor De La
author
Toral, Marta
author
Sánchez, Manuel
author
Gómez-Guzmán, Manuel
author
O'valle, Francisco
author
Jiménez, Rosario
author
Duarte, Juan
author
Romero, Miguel
funder
Ministerio de Economía y Competitividad (España)
funder
Regional Government of Andalusia (España)
funder
Instituto de Salud Carlos III
funder
University of Granada (España)
2020-06-09T12:15:01Z
2020-06-09T12:15:01Z
2020-07
J Hypertens. 2020; 38(7):1322-1335
10.1097/HJH.0000000000002368
1473-5598
Journal of hypertension
32004206
http://hdl.handle.net/20.500.12105/10306
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).
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.
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.
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.
eng
Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice.
journal article
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Toll-likeReceptor7-driven_2020.pdf.txt
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