Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice
Experimental & Molecular Medicine
; : 594-602, 2012.
Article
Dans En
| WPRIM
| ID: wpr-14963
Responsable en Bibliothèque :
WPRO
ABSTRACT
The incidence of cardiovascular disease is predicted to increase as the population ages. There is accumulating evidence that arginase upregulation is associated with impaired endothelial function. Here, we demonstrate that arginase II (ArgII) is upregulated in aortic vessels of aged mice and contributes to decreased nitric oxide (NO) generation and increased reactive oxygen species (ROS) production via endothelial nitric oxide synthase (eNOS) uncoupling. Inhibiting ArgII with small interfering RNA technique restored eNOS coupling to that observed in young mice and increased NO generation and decreased ROS production. Furthermore, enhanced vasoconstrictor responses to U46619 and attenuated vasorelaxation responses to acetylcholine in aged vasculature were markedly improved following siRNA treatment against ArgII. These results might be associated with increased L-arginine bioavailability. Collectively, these results suggest that ArgII may be a valuable target in age-dependent vascular diseases.
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Aorte
/
Arginase
/
Vasoconstriction
/
Vieillissement
/
Endothélium vasculaire
/
Régulation positive
/
Induction enzymatique
/
Espèces réactives de l'oxygène
/
Acide 15-hydroxy-11alpha,9alpha-(époxyméthano)prosta-5,13-diénoïque
/
Petit ARN interférent
Limites du sujet:
Animals
langue:
En
Texte intégral:
Experimental & Molecular Medicine
Année:
2012
Type:
Article