Repeated Porphyromonas gingivalis W83 exposure leads to release pro-inflammatory cytokynes and angiotensin II in coronary artery endothelial cells

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.

Porphyromonas gingivalis and Its Systemic Impact: Current Status

“…P. gingivalis has been reported to affect these processes and thereby promote hypertension. It was shown that repeated exposure of live P. gingivalis or bacteria LPS induced the release of pro-inflammatory CKs and angiotensin II in human coronary artery endothelial cells, together with P. gingivalis -associated mediators of systemic inflammation (such as CRP, IL-6, TNF-α), contributing to both endothelial dysfunction and the development of arterial hypertension [ 61 ]. Recently, an animal study supported the hypothesis that the Th1 immune response induced by P. gingivalis antigens is response for elevated BP [ 60 ].…”

Oral and Intestinal Bacterial Substances Associated with Disease Activities in Patients with Rheumatoid Arthritis: A Cross-Sectional Clinical Study

“…Locally produced GM-CSF activates sensory neurons expressing the GM-CSF receptor, transmitting painful stimuli to ascending nociceptive pathways in the spinal cord and brain [76,77]. Viafara-García et al reported that P. gingivalis or Pg-LPS treatment induced GM-CSF and angiotensin II production in coronary artery endothelial cells [78]. There might be a possibility that continual P. gingivalis influx from the oral cavity into the gut might be associated with patient pain due to increased GM-CSF levels.…”

Membrane vesicles from periodontal pathogens and their potential roles in periodontal disease and systemic illnesses

“…75 Etiologically, P. gingivalis could invade vascular endothelial cells and enhance pro-inflammatory chemokine production, and endothelial cell dysfunction promoted immune cell infiltration. 76 In physiological conditions, endothelial cells manufacture protective molecule NO, which enhances artery dilation and inhibits leukocyte adhesion. However, P. gingivalis-released OMVs suppressed the activity of endothelial nitric oxide synthase (eNOS), a speed-limiting enzyme for NO synthesis, and thus contributed to the development of atherosclerosis.…”