Farrugia, C. orcid.org/0000-0003-1318-8885, Stafford, G.P., Potempa, J. et al. (4 more authors) (2021) Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis. The FEBS Journal, 288 (5). pp. 1479-1495. ISSN 1742-464X
Abstract
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | cardiovascular disease; Porphyromonas gingivalis; endothelial cells; periodontal disease; gingipain |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Clinical Dentistry (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL BB/M012522/1 DIABETES UK 17/0005678 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 13 Aug 2020 09:06 |
Last Modified: | 21 Jan 2022 11:50 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1111/febs.15486 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:164322 |