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Regulación del glicoma y el transcriptoma de la vasculogénesis

Rania Harfouche¹, Dirk M Hentschel¹, Stephanie Piecewicz¹

¹Department of Medicine (R.H., D.M.H., S.P., S.B., S.S.), Brigham and Women's Hospital, Boston, Mass; Department of Molecular Medicine and Pathology (C.P.), University of Auckland, Auckland, New Zealand; Department of Biological Engineering (D.E., T.K., R.S.), Massachusetts Institute of Technology, Cambridge, Mass; and Harvard-MIT Division of Health Sciences and Technology (R.H., S.P., S.B., D.E., T.K., R.S., S.S.), Cambridge, Mass.

|October 28, 2009

Resumen

Este estudio revela cómo los glicosaminoglicanos del sulfato de heparan y la expresión génica interactúan para regular la formación de vasos sanguíneos (vasculogénesis). La modulación de estas interacciones ofrece potencial para la vascularización terapéutica en condiciones isquémicas.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología del desarrollo Biología del desarrollo.
Biología Molecular Biología Molecular

Sus antecedentes:

La vasculogénesis terapéutica es una estrategia prometedora para el tratamiento de enfermedades isquémicas.
El glicoma de la superficie celular, particularmente los glicosaminoglicanos de sulfato de heparan (HSG), y el transcriptoma se investigan por su papel en la regulación de la vasculogénesis.

Objetivo del estudio:

Para dilucidar la corregulación de la vasculogénesis por HSG y el transcriptoma.
Para explorar la interacción entre el glicoma y el transcriptoma durante la formación de vasos sanguíneos.

Principales métodos:

Diferenciación de las células madre embrionarias en células endoteliales.
La desactivación de la N-deacetilasa/N-sulfotransferasa 1 (NDST1) mediante el uso de ARN de pequeña horquilla.
Estudios in vivo con embriones de pez cebra.
Análisis de microarrays para identificar patrones de expresión génica.

Principales resultados:

La sulfatación de HSG, correlacionada con los niveles de NDST1, es crucial para la diferenciación de las células endoteliales.
La eliminación de NDST1 o la modificación de HSG alteraron la diferenciación de las células madre embrionarias y la vascularización del pez cebra.
El análisis de la expresión génica reveló vías que vinculan la regulación del glucocalicio con la señalización celular, la supervivencia y la determinación del destino, involucrando la caja O3A/5 de Forkhead y el factor de crecimiento similar a la insulina.

Conclusiones:

Este estudio demuestra una nueva interacción entre el glicoma y el transcriptoma durante la vasculogénesis.
Dirigirse a los gluco-microambientes celulares presenta una vía potencial para las estrategias de vascularización terapéutica.

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