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Los polimorfismos de plaquetas GP IIIa Pl(A) muestran diferentes sensibilidades a los agonistas
A D Michelson1, M I Furman, P Goldschmidt-Clermont
1Departments of Medicine and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Circulation
|March 7, 2000
Resumen
La variante del gen Pl(A2) en las plaquetas aumenta su reactividad y activación. Esta diferencia genética en la función plaquetaria puede explicar la predisposición hereditaria a los eventos coronarios.
Área de la Ciencia:
- Genética cardiovascular Genética cardiovascular Genética cardiovascular Genética cardiovascular Genética cardiovascular
- Hematología Hematología.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La predisposición hereditaria y la hiperreactividad plaquetaria están vinculadas a los eventos coronarios isquémicos.
- Los mecanismos subyacentes a las diferencias genéticas en la función plaquetaria siguen sin estar claros.
- El polimorfismo Pl(A2) de la glicoproteína IIIa (GP IIIa) está asociado con síndromes coronarios, lo que ha llevado a investigar su papel en la hiperreactividad plaquetaria.
Objetivo del estudio:
- Para caracterizar los parámetros funcionales de las plaquetas con el polimorfismo Pl(A) (HPA-1).
- Investigar el impacto de la sustitución de Leu (Pl (A1)) por Pro (Pl (A2)) en el GP IIIa en la activación y función plaquetaria.
- Determinar si la variante Pl(A2) contribuye a la hiperreactividad plaquetaria e influye en la respuesta a los agentes antiplaquetarios.
Principales métodos:
- Se estudiaron 56 donantes sanos genotipados para el polimorfismo Pl (A1,A1), Pl (A1,A2), Pl (A2,A2)).
- Se evaluó la P-selectina expresada en superficie, el fibrinógeno ligado al GP IIb/IIIa y el GP IIb/IIIa activado en respuesta al difosfato de adenosina (ADP).
- Sensibilidad evaluada de la agregación plaquetaria a la aspirina y al abciximab.
Principales resultados:
- Las plaquetas Pl(A2) positivas exhibieron un efecto de dosificación génica con una P-selectina significativamente mayor, la unión al fibrinógeno y la activación de GP IIb/IIIa tras la estimulación de la ADP en dosis bajas en comparación con las plaquetas Pl(A1,A1).
- La expresión de GP IIb/IIIa estimulada por ADP fue significativamente mayor en las plaquetas Pl(A2,A2).
- Las plaquetas heterocigotas para los alelos PlA (PlA1,A2) mostraron una mayor sensibilidad a la inhibición de la agregación de la aspirina y el abciximab.
Conclusiones:
- Las plaquetas Pl(A2) positivas demuestran un umbral reducido para la activación.
- Las plaquetas heterocigóticas Pl ((A) exhiben una mayor sensibilidad a los medicamentos antiplaquetarios comunes.
- Estos hallazgos in vitro sugieren una relevancia potencial para la comprensión de las condiciones trombóticas in vivo y la terapia antiplaquetaria personalizada.
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