Heme oxygenase attenuated angiotensin II-mediated increase in cyclooxygenase activity and decreased isoprostane F2alpha in endothelial cells.
Thromb Res
; 110(5-6): 305-9, 2003 Jun 15.
Article
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| MEDLINE
| ID: mdl-14592553
ABSTRACT
Heme oxygenase (HO) regulates cellular heme levels and catalyzes the formation of bilirubin and carbon monoxide (CO). We hypothesized that the status of the endothelial HO system influences the angiotensin (Ang) II-induced increase in the endothelial cell (EC) production of PGE2, eicosanoids which modulate the vascular actions of Ang II. In this study, we investigated the effect of interventions that suppress HO activity or induce HO-1 gene expression on Ang II-mediated increase in PGE2 in cultures of human microvessel endothelial cells (EC). Incubation of EC with Ang II (100 ng/ml) for 24 h increased the levels of PGE2 in the culture media. This effect of Ang II on prostaglandin production by EC was attenuated in cells treated with heme, but was magnified in cells treated with the HO inhibitor, Stannis mesoporphyrin (SnMP). Upregulation of HO-1 gene expression by retrovirus-mediated delivery of the human HO-1 gene attenuated heme and Ang II-induced prostaglandin synthesis. We also investigated the physiological significance of human HO-1 overexpression on attenuation of Ang II-mediated oxidative stress. Decreases in COMET levels were found in EC transduced with the HO-1 gene. These results indicate that overexpression of the HO system in EC exerts an inhibitory influence on Ang II-induced synthesis of prostaglandins and attenuates DNA damage caused by exposure to Ang II.
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Base de datos:
MEDLINE
Asunto principal:
Daño del ADN
/
Angiotensina II
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Prostaglandina-Endoperóxido Sintasas
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Células Endoteliales
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Hemo Oxigenasa (Desciclizante)
Idioma:
En
Revista:
Thromb Res
Año:
2003
Tipo del documento:
Article