Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
  • Additional Information
    • Affiliation:
      Department of Pharmacology, School of Pharmacy, University of Granada
      Gene Regulation in Cardiovascular Remodeling and Inflammation Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid
      CIBER-Enfermedades Cardiovasculares (CiberCV)
      Instituto de Investigación Biosanitaria de Granada (ibs.GRANADA)
      Department of Pathological Anatomy, School of Medicine, University of Granada
      Centro de Investigaciones Biomédicas (CIBM), Granada, Spain
      Iñaki Robles-Vera and Néstor De La Visitación contributed equally as first authors
    • 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.
    • Journal Subset:
      Biomedical; Expert Peer Reviewed; Peer Reviewed; USA
    • ISSN:
      0263-6352
    • MEDLINE Info:
      PMID: NLM32004206 NLM UID: 8306882
    • Publication Date:
      In Process
    • Publication Date:
      20200722
    • DOI:
      10.1097/HJH.0000000000002368
    • Accession Number:
      144661922
  • Citations
    • ABNT:
      ROBLES-VERA, I. et al. Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. Journal of Hypertension, [s. l.], v. 38, n. 7, p. 1322–1335, 2020. DOI 10.1097/HJH.0000000000002368. Disponível em: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144661922. Acesso em: 1 dez. 2020.
    • AMA:
      Robles-Vera I, De La Visitación N, Toral M, et al. Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. Journal of Hypertension. 2020;38(7):1322-1335. doi:10.1097/HJH.0000000000002368
    • APA:
      Robles-Vera, I., De La Visitación, N., Toral, M., Sánchez, M., Gómez-Guzmán, M., O’valle, F., Jiménez, R., Duarte, J., Romero, M., & Visitación, N. D. L. (2020). Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. Journal of Hypertension, 38(7), 1322–1335. https://doi.org/10.1097/HJH.0000000000002368
    • Chicago/Turabian: Author-Date:
      Robles-Vera, Iñaki, Néstor De La Visitación, Marta Toral, Manuel Sánchez, Manuel Gómez-Guzmán, Francisco O’valle, Rosario Jiménez, Juan Duarte, Miguel Romero, and Néstor De La Visitación. 2020. “Toll-like Receptor 7-Driven Lupus Autoimmunity Induces Hypertension and Vascular Alterations in Mice.” Journal of Hypertension 38 (7): 1322–35. doi:10.1097/HJH.0000000000002368.
    • Harvard:
      Robles-Vera, I. et al. (2020) ‘Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice’, Journal of Hypertension, 38(7), pp. 1322–1335. doi: 10.1097/HJH.0000000000002368.
    • Harvard: Australian:
      Robles-Vera, I, De La Visitación, N, Toral, M, Sánchez, M, Gómez-Guzmán, M, O’valle, F, Jiménez, R, Duarte, J, Romero, M & Visitación, NDL 2020, ‘Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice’, Journal of Hypertension, vol. 38, no. 7, pp. 1322–1335, viewed 1 December 2020, .
    • MLA:
      Robles-Vera, Iñaki, et al. “Toll-like Receptor 7-Driven Lupus Autoimmunity Induces Hypertension and Vascular Alterations in Mice.” Journal of Hypertension, vol. 38, no. 7, July 2020, pp. 1322–1335. EBSCOhost, doi:10.1097/HJH.0000000000002368.
    • Chicago/Turabian: Humanities:
      Robles-Vera, Iñaki, Néstor De La Visitación, Marta Toral, Manuel Sánchez, Manuel Gómez-Guzmán, Francisco O’valle, Rosario Jiménez, Juan Duarte, Miguel Romero, and Néstor De La Visitación. “Toll-like Receptor 7-Driven Lupus Autoimmunity Induces Hypertension and Vascular Alterations in Mice.” Journal of Hypertension 38, no. 7 (July 2020): 1322–35. doi:10.1097/HJH.0000000000002368.
    • Vancouver/ICMJE:
      Robles-Vera I, De La Visitación N, Toral M, Sánchez M, Gómez-Guzmán M, O’valle F, et al. Toll-like receptor 7-driven lupus autoimmunity induces hypertension and vascular alterations in mice. Journal of Hypertension [Internet]. 2020 Jul [cited 2020 Dec 1];38(7):1322–35. Available from: http://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=rzh&AN=144661922