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El coactivador-3 del receptor de esteroides es necesario para la inhibición de la formación de neointima por el
Yuhui Yuan1, Lan Liao, David A Tulis
1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Tex 77030, USA.
Circulation
|June 5, 2002
Resumen
El coactivador-3 del receptor de esteroides (SRC-3) es crucial para la protección mediada por estrógenos contra lesiones vasculares. Su ausencia perjudica el estrógeno estrogénico.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Endocrinología Molecular La Endocrinología Molecular
- Biología Vascular Biología Vascular
Sus antecedentes:
- Los receptores de estrógenos (RE) median los efectos vasoprotectores, que requieren coactivadores para la actividad transcripcional.
- El coactivador-3 del receptor de esteroides (SRC-3) interactúa con las ER y mejora la transcripción del gen diana.
- Este estudio investiga la expresión de SRC-3 en el tejido cardiovascular y su papel en la vasoprotección dependiente del estrógeno.
Objetivo del estudio:
- Para caracterizar el patrón de expresión de SRC-3 dentro del sistema cardiovascular.
- Para aclarar el papel de SRC-3 en la protección mediada por estrógenos contra la lesión vascular y la remodelación.
Principales métodos:
- La expresión de SRC-3 se analizó en los tejidos cardiovasculares de ratones SRC-3(+/-) utilizando la tinción X-gal.
- La remodelación vascular se evaluó en ratones SRC-3(-/-) y de tipo salvaje utilizando un modelo de ligadura carotídea unilateral.
- Se evaluó el impacto de la ovariectomía y el tratamiento con estrógenos en la formación de neointima y la proliferación de células vasculares.
Principales resultados:
- SRC-3 se detectó en el músculo liso vascular y las células endoteliales, pero no en las células del miocardio.
- Los ratones SRC-3(-/-) exhibieron una formación de neointima significativamente mayor en comparación con los ratones de tipo salvaje, un efecto dependiente de los niveles de estrógeno.
- El tratamiento con estrógenos restauró parcialmente la inhibición del crecimiento neoinimal y la proliferación de células vasculares en ratones SRC-3.
Conclusiones:
- SRC-3 es altamente expresado en las células vasculares y juega un papel importante en la vasoprotección mediada por estrógenos.
- La pérdida de la función SRC-3 reduce la eficacia de los estrógenos en la inhibición del crecimiento neoinimal, probablemente debido a la disminución de la supresión de la proliferación celular vascular.
- SRC-3 es esencial para facilitar los efectos vasoprotectores dependientes de ER durante el trauma vascular.
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