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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

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Authors

Cher Farrugia

Graham P. Stafford

Jan Potempa

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

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