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El factor de necrosis tumoral alfa promueve la calcificación in vitro de las células vasculares a través de la vía
1Division of Cardiology, Departments of Medicine and Physiology, UCLA School of Medicine, Los Angeles, CA 90095-1679, USA. ytintut@ucla.edu
Circulation
|November 22, 2000
Resumen
El factor de necrosis tumoral alfa (TNF-alfa) promueve la calcificación vascular al inducir la diferenciación osteoblástica en las células vasculares. Este proceso implica la vía cAMP y mejora la mineralización de la matriz, lo que sugiere un papel para el TNF-alfa en la aterosclerosis.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- Biología celular Biología celular.
- La bioquímica es la bioquímica.
Sus antecedentes:
- La calcificación vascular es una característica de la aterosclerosis.
- El factor de necrosis tumoral alfa (TNF-alfa), una citocina en las lesiones ateroscleróticas, regula la formación ósea.
- El papel del TNF-alfa en la calcificación vascular requiere investigación.
Objetivo del estudio:
- Para investigar el papel del TNF-alfa en la calcificación vascular in vitro.
- Para determinar si el TNF-alfa promueve la diferenciación osteoblástica de las células vasculares.
Principales métodos:
- Las células del músculo liso de la aorta bovina fueron tratadas con TNF-alfa.
- Se evaluó la diferenciación y mineralización osteoblástica utilizando la actividad de la fosfatasa alcalina y la incorporación de calcio.
- Se analizaron los niveles de inhibidor de la proteína quinasa A (KT5720) y de cAMP.
- El ensayo de desplazamiento de movilidad electroforética identificó la unión del factor de transcripción.
Principales resultados:
- TNF-alfa indujo una morfología similar a la de los osteoblastos y mejoró la actividad de la fosfatasa alcalina y la expresión de ARNm.
- El tratamiento continuo con TNF-alfa aumentó la mineralización de la matriz.
- La inhibición de la proteína quinasa A atenuó los efectos inducidos por el TNF-alfa.
- El TNF-alfa elevó los niveles intracelulares de cAMP y aumentó la unión al ADN de Osf2, AP1 y CREB.
Conclusiones:
- El TNF-alfa promueve la calcificación vascular in vitro.
- Este efecto está mediado por la promoción de la diferenciación osteoblástica en las células vasculares.
- La vía cAMP está involucrada en la calcificación vascular inducida por el TNF-alfa.
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