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La inhibición de la función de la integrina por un péptido cíclico que contiene RGD previene la formación de
H Matsuno1, J M Stassen, J Vermylen
1Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
Circulation
|November 1, 1994
Resumen
Los péptidos cíclicos que contienen RGD inhiben la formación de neointima al bloquear la función de la integrina. La administración temprana y continua de estos péptidos es la más efectiva para prevenir las complicaciones de la lesión vascular.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Integración de la señalización integrin.
- Biología Vascular Biología Vascular
Sus antecedentes:
- Los péptidos que contienen RGD inhiben la unión de la integrina a los ligandos.
- Las integrinas alfa IIb beta 3 y alfa v beta 3 están implicadas en la agregación plaquetaria y la migración celular del músculo liso.
- La agregación plaquetaria y la migración de las células musculares lisas contribuyen a la formación de neointima.
Objetivo del estudio:
- Para investigar la eficacia de un péptido cíclico que contiene RGD (G4120) en la inhibición de la formación de neointima.
- Determinar el momento y la duración óptimos de la administración de G4120 para la prevención de la neointima.
Principales métodos:
- La lesión vascular fue inducida en las arterias carótidas del hámster.
- G4120 se administró por vía intravenosa a través de la bomba osmótica en diferentes momentos y duraciones.
- La formación de neointima se cuantificó en diferentes momentos posteriores a la lesión.
Principales resultados:
- G4120 inhibió significativamente la formación de neointima de una manera dependiente de la dosis.
- La administración continua comenzando antes de la lesión vascular produjo la inhibición más fuerte.
- El retraso o la reducción de la duración del tratamiento fueron menos efectivos.
Conclusiones:
- La inhibición de la función de la integrina con péptidos que contienen RGD reduce el desarrollo de la neointima.
- La inhibición temprana puede implicar el bloqueo de la agregación plaquetaria y la secreción de PDGF (alfa IIb beta 3).
- La inhibición tardía puede implicar interferencia con la migración de las células del músculo liso (alfa v beta 3).
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