Porphyromonas gingivalis triggers the shedding of inflammatory endothelial microvesicles that act as autocrine effectors of endothelial dysfunction

• Published in: Scientific reports Vol. 10; no. 1; p. 1778
• Main Authors: Bugueno, Isaac Maximiliano, Zobairi El-Ghazouani, Fatiha, Batool, Fareeha, El Itawi, Hanine, Anglès-Cano, Eduardo, Benkirane-Jessel, Nadia, Toti, Florence, Huck, Olivier
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04-02-2020; Nature Publishing Group
• Subjects: 13; 13/106; 13/21; 13/31; 38/77; 692/420/254; 692/420/256/2515; 82/79; AKT protein; Apoptosis; Autocrine signalling; Bacteria; Bacteroidaceae Infections - metabolism; Cardiology and cardiovascular system; Cell-Derived Microparticles - metabolism; Cell-Derived Microparticles - microbiology; Cytokines - metabolism; Disease; Endothelial cells; Endothelial Cells - metabolism; Endothelial Cells - microbiology; Gene expression; Homeostasis; Human health and pathology; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - microbiology; Humanities and Social Sciences; Humans; Infections; Infectious diseases; Inflammation; Inflammation - metabolism; Inflammation - microbiology; Intercellular adhesion molecule 1; Intercellular Adhesion Molecule-1 - metabolism; Interleukin 6; Interleukin 8; Life Sciences; multidisciplinary; Nitric Oxide Synthase Type II - metabolism; Nitric Oxide Synthase Type III - metabolism; Nitric-oxide synthase; Oxidative Stress - physiology; Paracrine signalling; Periodontitis; Porphyromonas gingivalis; Prothrombinase; Science; Science (multidisciplinary); Tumor necrosis factor-α; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - metabolism
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-58374-z

A link between periodontitis and atherothrombosis has been highlighted. The aim of this study was to determine the influence of
Porphyromonas gingivalis
on endothelial microvesicles (EMV
Pg
) shedding and their contribution to endothelial inflammation. Endothelial cells (EC) were infected with
P. gingivalis
(MOI = 100) for 24 h. EMV
Pg
were isolated and their concentration was evaluated by prothrombinase assay. EMV
Pg
were significantly increased in comparison with EMV
Ctrl
shedded by unstimulated cells. While EMV
Ctrl
from untreated EC had no effect, whereas, the proportion of apoptotic EC was increased by 30 nM EMV
Pg
and viability was decreased down to 25%, a value elicited by
P. gingivalis
alone. Moreover, high concentration of EMV
Pg
(30 nM) induced a pro-inflammatory and pro-oxidative cell response including up-regulation of TNF-α, IL-6 and IL-8 as well as an altered expression of iNOS and eNOS at both mRNA and protein level. An increase of VCAM-1 and ICAM-1 mRNA expression (4.5 folds and 3 folds respectively (
p
 < 0.05 vs untreated) was also observed after EMV
Pg
(30 nM) stimulation whereas
P. gingivalis
infection was less effective, suggesting a specific triggering by EMV
Pg
. Kinasome analysis demonstrated the specific effect induced by EMV
Pg
on main pro-inflammatory pathways including JNK/AKT and STAT. EMV
Pg
are effective pro-inflammatory effectors that may have detrimental effect on vascular homeostasis and should be considered as potential autocrine and paracrine effectors involved in the link between periodontitis and atherothrombosis.