Opposing actions of Notch1 and VEGF in post-natal cardiac valve endothelial cells.
Biochem Biophys Res Commun
; 374(3): 512-6, 2008 Sep 26.
Article
em En
| MEDLINE
| ID: mdl-18647596
ABSTRACT
The endothelium of the cardiac valves is unique compared the rest of the vasculature in its ability to undergo an endothelial-to-mesenchymal transformation (EMT) in vitro in response to transforming growth factor-beta (TGF-beta). EMT is a critical event during embryonic valve development, and both VEGF-A and Notch1 have been shown to function in this process. Here we investigate the effects of VEGF-A and Notch1 on EMT in clonal endothelial cell (EC) populations isolated from adult aortic valve leaflets. VEGF-A inhibited TGF-beta-induced EMT. Endothelial growth, however, was not affected by VEGF-A or TGF-beta. A positive role for Notch1 was revealed in three experiments (1) TGF-beta induced Notch1 mRNA in valve ECs, (2) a gamma-secretase inhibitor of Notch1 signaling blocked EMT, and (3) overexpression of a ligand-independent form of Notch1 induced EMT. These results demonstrate, for the first time, that VEGF-A and Notch1 play opposing roles in regulating EMT in post-natal valve endothelium.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Valva Aórtica
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Endotélio Vascular
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Fator A de Crescimento do Endotélio Vascular
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Receptor Notch1
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Mesoderma
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article