RESUMEN
Porphyromonas gingivalis is a bacterial species that causes destruction of periodontal tissues. Additionally, previous evidence indicates that GroEL from P. gingivalis may possess biological activities involved in systemic inflammation, especially inflammation involved in the progression of periodontal diseases. The literature has established a relationship between periodontal disease and cancer. However, it is unclear whether P. gingivalis GroEL enhances tumor growth. Here, we investigated the effects of P. gingivalis GroEL on neovasculogenesis in C26 carcinoma cell-carrying BALB/c mice and chick eggs in vivo as well as its effect on human endothelial progenitor cells (EPC) in vitro. We found that GroEL treatment accelerated tumor growth (tumor volume and weight) and increased the mortality rate in C26 cell-carrying BALB/c mice. GroEL promoted neovasculogenesis in chicken embryonic allantois and increased the circulating EPC level in BALB/c mice. Furthermore, GroEL effectively stimulated EPC migration and tube formation and increased E-selectin expression, which is mediated by eNOS production and p38 mitogen-activated protein kinase activation. Additionally, GroEL may enhance resistance against paclitaxel-induced cell cytotoxicity and senescence in EPC. In conclusion, P. gingivalis GroEL may act as a potent virulence factor, contributing to the neovasculogenesis of tumor cells and resulting in accelerated tumor growth.
Asunto(s)
Proteínas Bacterianas/metabolismo , Chaperonina 60/metabolismo , Neoplasias del Colon/microbiología , Células Progenitoras Endoteliales/metabolismo , Porphyromonas gingivalis/patogenicidad , Alantoides/irrigación sanguínea , Animales , Línea Celular Tumoral , Embrión de Pollo , Selectina E/metabolismo , Células Progenitoras Endoteliales/citología , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Microscopía Confocal , Neovascularización Fisiológica , Óxido Nítrico Sintasa de Tipo III/metabolismo , Fosforilación , Porphyromonas gingivalis/genética , Proteínas Recombinantes/metabolismo , Factores de Virulencia/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
BACKGROUND: Verapamil is an effective vasodilator. The purpose of this study was to investigate the in vivo effect of verapamil on coronary blood flow velocity and vascular resistance in anesthetized, open-chest rabbits. METHODS: Twenty-one male New Zealand white rabbits were anesthetized, and a 3-mm suction-type pulsed Doppler velocimeter probe was applied to the proximal part of the left anterior descending coronary artery after median sternotomy. The rabbits received intravenous bolus infusion of 4 different doses of verapamil (0.01 mg/kg, n = 5; 0.1 mg/kg, n = 5; 1 mg/kg, n = 5, and 10 mg/kg, n = 6). The percent changes in coronary blood flow velocity and coronary vascular resistance were examined. RESULTS: There was 10.0+/-1.6% increase in coronary blood flow (CBF) and 12.5+/-1.9% reduction in coronary vascular resistance (CVR) after infusion of 0.01 mg/kg of verapamil. The CBF increased 23.0+/-9.5% and CVR decreased 24.2+/-5.2% after infusion of 0.1 mg/kg of verapamil. Infusion of 1 mg/kg of verapamil induced 34.8+/-10.5% increase in CBF and 32.6+/-2.5% reduction in CVR. The CBF increased 41.1+/-14.8% and CVR decreased 45.1+/-5.4% after infusion of 10 mg/kg of verapamil. CONCLUSIONS: Compared with baseline condition, all doses of verapamil increased coronary blood flow velocity and decreased coronary vascular resistance significantly in anesthetized, open-chest rabbits.