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 |
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| 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: | Graham, Dr Delyth and Czesnikiewicz-Guzik, Dr Marta and Vidler, Francesca and Harrison, Professor David and Guzik, Professor Tomasz and Nosalski, Dr Ryszard and Mikolajczyk, Dr Tomasz |
| 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 > School of Cardiovascular & Metabolic Health 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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