Dynamic regulation of the cerebral cavernous malformation pathway controls vascular stability and growth.
Dev Cell
; 23(2): 342-55, 2012 Aug 14.
Article
en En
| MEDLINE
| ID: mdl-22898778
ABSTRACT
Cardiovascular growth must balance stabilizing signals required to maintain endothelial connections and network integrity with destabilizing signals that enable individual endothelial cells to migrate and proliferate. The cerebral cavernous malformation (CCM) signaling pathway utilizes the adaptor protein CCM2 to strengthen endothelial cell junctions and stabilize vessels. Here we identify a CCM2 paralog, CCM2L, that is expressed selectively in endothelial cells during periods of active cardiovascular growth. CCM2L competitively blocks CCM2-mediated stabilizing signals biochemically, in cultured endothelial cells, and in developing mice. Loss of CCM2L reduces endocardial growth factor expression and impairs tumor growth and wound healing. Our studies identify CCM2L as a molecular mechanism by which endothelial cells coordinately regulate vessel stability and growth during cardiovascular development, as well as postnatal vessel growth.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Malformaciones Vasculares del Sistema Nervioso Central
/
Proteínas de Microfilamentos
/
Proteínas Asociadas a Microtúbulos
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Dev Cell
Asunto de la revista:
EMBRIOLOGIA
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos