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Sci Rep ; 9(1): 19379, 2019 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-31852912

RESUMO

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-1ß and MCP-1 were determined by RT-qPCR, and IL-6, MCP-1, IL-8, IL-1ß 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-1ß (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.


Assuntos
Angiotensina II/metabolismo , Aterosclerose/metabolismo , Hipertensão/metabolismo , Periodontite/etiologia , Porphyromonas gingivalis/metabolismo , Angiotensina II/genética , Aterosclerose/microbiologia , Aterosclerose/patologia , Quimiocina CCL2/genética , Vasos Coronários/metabolismo , Vasos Coronários/microbiologia , Vasos Coronários/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/microbiologia , Citometria de Fluxo , Regulação da Expressão Gênica/efeitos dos fármacos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Hipertensão/microbiologia , Hipertensão/patologia , Inflamação/genética , Inflamação/metabolismo , Inflamação/microbiologia , Inflamação/patologia , Interleucina-6/genética , Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/farmacologia , Periodontite/genética , Periodontite/metabolismo , Periodontite/microbiologia , Porphyromonas gingivalis/patogenicidade , RNA Mensageiro/genética , Receptor Tipo 1 de Angiotensina/genética
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