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Los receptores funcionales de nucleótidos P2Y2 median la hiperplasia íntima inducida por 5'-trifosfato de uridina en

Cheikh I Seye¹, Qiongman Kong, Laurie Erb

¹Department of Biochemistry, University of Missouri-Columbia, Columbia, Mo 65212, USA. seyec@missouri.edu

|November 20, 2002

Resumen

La uridina extracelular 5'-trifosfato (UTP) y la adenosina 5'-trifosfato (ATP) activan los receptores P2Y2, promoviendo la proliferación de las células del músculo liso y la hiperplasia íntima. Este estudio demuestra que el receptor P2Y2

Área de la Ciencia:

Biología Vascular Biología Vascular
La señalización celular de las células.
La medicina molecular es una medicina molecular.

Sus antecedentes:

La uridina 5'-trifosfato extracelular (UTP) activa las células del músculo liso (SMC) a través de los receptores de nucleótidos P2Y2.
El ARNm del receptor P2Y2 está elevado en lesiones íntimas, pero se desconoce su papel en la hiperplasia íntima.

Objetivo del estudio:

Para investigar el papel de los receptores P2Y2 en la lesión vascular y la hiperplasia íntima.
Para determinar si la activación del receptor P2Y2 contribuye a la proliferación de SMC y la formación de neointima.

Principales métodos:

Se utilizó un modelo de collar de silicona para inducir lesiones vasculares en las arterias carótidas de conejos.
Las imágenes de Fura-2 evaluaron los cambios en la concentración de calcio en las SMC en respuesta a los agonistas de los receptores P2Y.
La expresión de osteopontin se midió en respuesta a UTP y ATP, con el oligonucleótido antisentido P2Y2 utilizado para inhibir la expresión.

Principales resultados:

La colocación del cuello regulaba al alza el ARNm del receptor P2Y2 en las SMC antes de la formación de la neointima.
UTP y ATP, pero no UDP, aumentaron el calcio intracelular, lo que confirma la regulación al alza del receptor P2Y2 funcional.
La infusión perivascular de UTP mejoró significativamente el desarrollo neointimal y la infiltración de macrófagos.
La UTP y el ATP estimulan la expresión de osteopontina en las SMC, un efecto inhibido por el oligonucleótido antisentido P2Y2.

Conclusiones:

El receptor P2Y2 juega un papel importante en el desarrollo de la hiperplasia íntima.
Los hallazgos sugieren que la activación del receptor P2Y2 contribuye a la aterosclerosis y la restenosis.
Dirigirse a los receptores P2Y2 puede ofrecer una estrategia terapéutica para las enfermedades vasculares proliferativas.

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