Rap1 promotes endothelial mechanosensing complex formation, NO release and normal endothelial function.
EMBO Rep
; 16(5): 628-37, 2015 May.
Article
em En
| MEDLINE
| ID: mdl-25807985
ABSTRACT
Decreased nitric oxide (NO) bioavailability underlies a number of cardiovascular pathologies, including hypertension. The shear stress exerted by flowing blood is the main determinant of NO release. Rap1 promotes integrin- and cadherin-mediated signaling. Here, we show that Rap1 is a critical regulator of NO production and endothelial function. Rap1 deficiency in murine endothelium attenuates NO production and diminishes NO-dependent vasodilation, leading to endothelial dysfunction and hypertension, without deleterious effects on vessel integrity. Mechanistically, Rap1 is activated by shear stress, promotes the formation of the endothelial mechanosensing complex-comprised of PECAM-1, VE-cadherin and VEGFR2- and downstream signaling to NO production. Our study establishes a novel paradigm for Rap1 as a regulator of mechanotransduction.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas rap1 de Ligação ao GTP
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Mecanotransdução Celular
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Endotélio
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Óxido Nítrico
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
EMBO Rep
Ano de publicação:
2015
Tipo de documento:
Article