Th1 type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II dependent hypertension and vascular dysfunction

Czesnikiewicz-Guzik, M., Nosalski, R., Mikolajczyk, T. P., Vidler, F., Dohnal, T., Dembowska, E., Graham, D. , Harrison, D. G. and Guzik, T. J. (2019) Th1 type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II dependent hypertension and vascular dysfunction. British Journal of Pharmacology, 176(12), pp. 1922-1931. (doi:10.1111/bph.14536) (PMID:30414380) (PMCID:PMC6534780)

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Abstract

Background and Purpose: Emerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate blood pressure elevation, vascular inflammation and vascular dysfunction. Experimental Approach: Th1 immune response were elicited through immunizations using Porphyromonas gingivalis lysate antigens (10ug) conjugated with aluminium oxide (50ug) and IL‐12 (1ug). The hypertension and vascular endothelial dysfunction evoked by sub‐pressor doses of Angiotensin II (0.25mg/kg/day) were studied and vascular inflammation was quantified by flow cytometry and real time polymerase chain reaction. Key Results: Systemic T cell activation, characteristic for hypertension, was exacerbated by P. gingivalis antigen stimulations. This translated into increased aortic vascular inflammation with enhanced leukocytes, in particular, T cell and macrophage infiltration. Expression of the Th1 cytokines, Interferon‐γ and Tumour Necrosis Factor‐α and the transcription factor TBX21 was increased in aortas of P. gingivalis/Interleukin‐12/aluminium oxide immunized mice, while IL‐4 and TGF‐β were unchanged. These immune changes in mice with induced T helper type 1 immune responses were associated with enhanced blood pressure elevation and endothelial dysfunction compared to control mice in response to two weeks infusion of a sub‐pressor dose of Angiotensin II. Conclusion and Implications: These studies support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to sub‐pressor pro‐hypertensive insults such as low dose Angiotensin II, therefore providing a mechanistic link between chronic infection such as periodontitis and hypertension.

Item Type:Articles
Additional Information:The paper is supported by Marie Curie CIG Marie Curie CIG (Nr 631773); European Research Council (726318 to TJG) as well as the BHF Centre of Research Excellence (RE/13/5/30177), National Institutes of Health (NIH) Grants HL-390006, AR-42527, AI-44142, EY-11916, AR-41974, NIH Program Project Grants HL-58000 and P01075209.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Nosalski, Mr Ryszard and Czesnikiewicz-Guzik, Dr Marta and Vidler, Francesca and Mikolajczyk, Dr Tomasz and Guzik, Professor Tomasz and Graham, Dr Delyth and Harrison, Professor David
Authors: Czesnikiewicz-Guzik, M., Nosalski, R., Mikolajczyk, T. P., Vidler, F., Dohnal, T., Dembowska, E., Graham, D., Harrison, D. G., and Guzik, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:British Journal of Pharmacology
Publisher:Wiley
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:10 November 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in British Journal of Pharmacology 176(12):1922-1931
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
651771ImmunoTensionTomasz GuzikEuropean Commission (EC)631773RI CARDIOVASCULAR & MEDICAL SCIENCES
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES

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