Abstract
The role of Porphyromonas gingivalis (P. gingivalis) or its virulence factors, including lipopolysaccharide (LPS) not only has been related with periodontitis but also with endothelial dysfunction, a key mechanism involved in the genesis of atherosclerosis and hypertension that involving systemic inflammatory markers as angiotensin II (Ang II) and cytokines. This study compares the effect of repeated and unique exposures of P. gingivalis W83 LPS and live bacteria on the production and expression of inflammatory mediators and vasoconstrictor molecules with Ang II. Human coronary artery endothelial cells (HCAEC) were stimulated with purified LPS of P. gingivalis (1.0, 3.5 or 7.0 μg/mL) or serial dilutions of live bacteria (MOI 1: 100 - 1:0,1) at a single or repeated exposure for a time of 24 h. mRNA expression levels of AGTR1, AGTR2, IL-8, IL-1β and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1β and GM-CSF levels were measured by flow cytometry, ELISA determined Ang II levels. Live bacteria in a single dose increased mRNA levels of AGTR1, and repeated doses increased mRNA levels of IL-8 and IL-1β (p < 0.05). Repeated exposure of live-P. gingivalis induced significant production IL-6, MCP-1 and GM-CSF (p < 0.05). Moreover, these MCP-1, IL-6 and GM-CSF levels were greater than in cells treated with single exposure (p < 0.05), The expression of AGTR1 and production of Ang II induced by live-P. gingivalis W83 showed a vasomotor effect of whole bacteria in HCAEC more than LPS. In conclusion, the findings of this study suggest that repeated exposure of P. gingivalis in HCAEC induces the activation of proinflammatory and vasoconstrictor molecules that lead to endothelial dysfunction being a key mechanism of the onset and progression of arterial hypertension and atherosclerosis.
Highlights
Chronic systemic inflammation induced by periodontitis is linked to endothelial dysfunction due to the entry of Gram-negative anaerobes into the bloodstream after various stimuli, such as tooth brushing and chewing[3] and periodontal treatment[3,4,5] likewise, DNA6,7 of periodontal pathogens (e.g., Porphyromonas gingivalis) and live bacteria[8,9] have been demonstrated in atherosclerotic coronary lesions[10,11], and increased systemic inflammatory markers induced by endotoxemia have been associated with hypertension/early atherosclerosis and periodontal disease[12,13]
In relation to cell viability, our results demonstrated that LPS and live bacteria did not affect Human coronary artery endothelial cells (HCAEC) (Fig. 1)
We evaluated the expression of proinflammatory cytokine mRNA and AGTR genes in HCAEC stimulated with P. gingivalis-LPS and live-P. gingivalis W83
Summary
Chronic systemic inflammation induced by periodontitis is linked to endothelial dysfunction due to the entry of Gram-negative anaerobes into the bloodstream after various stimuli, such as tooth brushing and chewing[3] and periodontal treatment[3,4,5] likewise, DNA6,7 of periodontal pathogens (e.g., Porphyromonas gingivalis) and live bacteria[8,9] have been demonstrated in atherosclerotic coronary lesions[10,11], and increased systemic inflammatory markers induced by endotoxemia have been associated with hypertension/early atherosclerosis and periodontal disease[12,13]. P. gingivalis, a major periodontal pathogen in periodontitis, has been shown to stimulate cytokine/chemokine production, which induces expression of cell adhesion molecules, including intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1) and p-selectin, which are considered key steps in the onset of endothelial dysfunction[17,18]. The evolving role of Ang II as a regulator of endothelial cell function and its action by stimulating various receptors, angiotensin II type 1 receptor (AGTR1) stimulates oxidative stress, fibrosis, cell proliferation and a release of cytokines and chemokines which in turn mediates tissue inflammation[21,22]. The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) activation[21,22], that could lead to an increase in blood pressure, a decrease in nitric oxide, inflammation and development of atherosclerosis and endothelial dysfunction[22,24,25]
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