Cher Farrugia
Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis
Farrugia, Cher; Stafford, Graham P.; Potempa, Jan; Wilkinson, Robert N.; Chen, Yan; Murdoch, Craig; Widziolek, Magdalena
Authors
Graham P. Stafford
Jan Potempa
Dr ROB WILKINSON Rob.Wilkinson@nottingham.ac.uk
Assistant Professor
Yan Chen
Craig Murdoch
Magdalena Widziolek
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 (?K/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 ?K/R-ab. In agreement, when transgenic zebrafish larvae expressing fluorescently labelled PECAM-1 or VE-cadherin were systemically infected with W83 or ?K/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.
Citation
Farrugia, C., Stafford, G. P., Potempa, J., Wilkinson, R. N., Chen, Y., Murdoch, C., & Widziolek, M. (2021). Mechanisms of vascular damage by systemic dissemination of the oral pathogen Porphyromonas gingivalis. FEBS Journal, 288(5), 1479-1495. https://doi.org/10.1111/febs.15486
Journal Article Type | Article |
---|---|
Acceptance Date | Jul 14, 2020 |
Online Publication Date | Jul 18, 2020 |
Publication Date | 2021-03 |
Deposit Date | Aug 3, 2020 |
Publicly Available Date | Mar 29, 2024 |
Journal | The FEBS Journal |
Print ISSN | 1742-464X |
Electronic ISSN | 1742-4658 |
Publisher | Wiley |
Peer Reviewed | Peer Reviewed |
Volume | 288 |
Issue | 5 |
Pages | 1479-1495 |
DOI | https://doi.org/10.1111/febs.15486 |
Keywords | Cell Biology; Biochemistry; Molecular Biology |
Public URL | https://nottingham-repository.worktribe.com/output/4808433 |
Publisher URL | https://febs.onlinelibrary.wiley.com/doi/full/10.1111/febs.15486 |
Additional Information | Received: 2020-04-18; Accepted: 2020-07-14; Published: 2020-08-01 |
Files
febs.15486
(7.6 Mb)
PDF
Publisher Licence URL
https://creativecommons.org/licenses/by/4.0/
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