An antiangiogenic neurokinin-B/thromboxane A2 regulatory axis.
J Cell Biol
; 174(7): 1047-58, 2006 Sep 25.
Article
en En
| MEDLINE
| ID: mdl-17000881
ABSTRACT
Establishment of angiogenic circuits that orchestrate blood vessel development and remodeling requires an exquisite balance between the activities of pro- and antiangiogenic factors. However, the logic that permits complex signal integration by vascular endothelium is poorly understood. We demonstrate that a "neuropeptide," neurokinin-B (NK-B), reversibly inhibits endothelial cell vascular network assembly and opposes angiogenesis in the chicken chorioallantoic membrane. Disruption of endogenous NK-B signaling promoted angiogenesis. Mechanistic analyses defined a multicomponent pathway in which NK-B signaling converges upon cellular processes essential for angiogenesis. NK-B-mediated ablation of Ca2+ oscillations and elevation of 3'-5' [corrected] cyclic adenosine monophosphate (cAMP) reduced cellular proliferation, migration, and vascular endothelial growth factor receptor expression and induced the antiangiogenic protein calreticulin. Whereas NK-B initiated certain responses, other activities required additional stimuli that increase cAMP. Although NK-B is a neurotransmitter/ neuromodulator and NK-B overexpression characterizes the pregnancy-associated disorder preeclampsia, NK-B had not been linked to vascular remodeling. These results establish a conserved mechanism in which NK-B instigates multiple activities that collectively oppose vascular remodeling.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tromboxano A2
/
Neuroquinina B
/
Transducción de Señal
/
Inhibidores de la Angiogénesis
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Cell Biol
Año:
2006
Tipo del documento:
Article
País de afiliación:
Estados Unidos