Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis.

Autor: Farrugia C; School of Clinical Dentistry, University of Sheffield, UK., Stafford GP; School of Clinical Dentistry, University of Sheffield, UK., Potempa J; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.; Department of Oral Immunity and Infectious Diseases, University of Louisville School of Dentistry, KY, USA., Wilkinson RN; School of Life Sciences, Medical School, University of Nottingham, UK., Chen Y; Department of Infection, Immunity and Cardiovascular Disease, Medical School, University of Sheffield, UK., Murdoch C; School of Clinical Dentistry, University of Sheffield, UK., Widziolek M; School of Clinical Dentistry, University of Sheffield, UK.; Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.; Department of Evolutionary Immunology, Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland.
Jazyk: angličtina
Zdroj: The FEBS journal [FEBS J] 2021 Mar; Vol. 288 (5), pp. 1479-1495. Date of Electronic Publication: 2020 Aug 01.
DOI: 10.1111/febs.15486
Abstrakt: Several studies have shown a clear association between periodontal disease and increased risk of cardiovascular disease. Porphyromonas gingivalis (Pg), a key oral pathogen, and its cell surface-expressed gingipains, induce oedema in a zebrafish larvae infection model although the mechanism of these vascular effects is unknown. Here, we aimed to determine whether Pg-induced vascular damage is mediated by gingipains. In vitro, human endothelial cells from different vascular beds were invaded by wild-type (W83) but not gingipain-deficient (ΔK/R-ab) Pg. W83 infection resulted in increased endothelial permeability as well as decreased cell surface abundance of endothelial adhesion molecules PECAM-1 and VE-cadherin compared to infection with ΔK/R-ab. In agreement, when transgenic zebrafish larvae expressing fluorescently labelled PECAM-1 or VE-cadherin were systemically infected with W83 or ΔK/R-ab, a significant reduction in adhesion molecule fluorescence was observed specifically in endothelium proximal to W83 bacteria through a gingipain-dependent mechanism. Furthermore, this was associated with increased vascular permeability in vivo when assessed by dextran leakage microangiography. These data are the first to show that Pg directly mediates vascular damage in vivo by degrading PECAM-1 and VE-cadherin. Our data provide a molecular mechanism by which Pg might contribute to cardiovascular disease.
(© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
Databáze: MEDLINE
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