Perivascular delivery of Notch 1 siRNA inhibits injury-induced arterial remodeling.
PLoS One
; 9(1): e84122, 2014.
Article
em En
| MEDLINE
| ID: mdl-24416200
ABSTRACT
OBJECTIVES:
To determine the efficacy of perivascular delivery of Notch 1 siRNA in preventing injury-induced arterial remodeling. METHODS ANDRESULTS:
Carotid artery ligation was performed to induce arterial remodeling. After 14 days, morphometric analysis confirmed increased vSMC growth and subsequent media thickening and neointimal formation. Laser capture microdissection, quantitative qRT-PCR and immunoblot analysis of medial tissue revealed a significant increase in Notch1 receptor and notch target gene, Hrt 1 and 2 expression in the injured vessels. Perivascular delivery of Notch 1 siRNA by pluronic gel inhibited the injury-induced increase in Notch 1 receptor and target gene expression when compared to scrambled siRNA controls while concomitantly reducing media thickening and neointimal formation to pre-injury, sham-operated levels. Selective Notch 1 knockdown also reversed the injury-induced inhibition of pro-apoptotic Bax expression while decreasing injury-induced anti-apoptotic Bcl-XL expression to sham-operated control levels. In parallel experiments, proliferative cyclin levels, as measured by PCNA expression, were reversed to sham-operated control levels following selective Notch 1 knockdown.CONCLUSION:
These results suggest that injury-induced arterial remodeling can be successfully inhibited by localized perivascular delivery of Notch 1 siRNA.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Técnicas de Transferência de Genes
/
Lesões das Artérias Carótidas
/
RNA Interferente Pequeno
/
Receptor Notch1
Limite:
Animals
Idioma:
En
Revista:
PLoS One
Ano de publicação:
2014
Tipo de documento:
Article