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La aortopatía torácica inducida por β-aminopropionitril es refractaria al cilostazol y al sildenafil en ratones
Samuel C Tyagi1,2,3,4, Sohei Ito1,2, Jacob C Hubbuch1,2,3,4
1Saha Cardiovascular Research Center, College of Medicine, University of Kentucky, Lexington, Kentucky, United States of America.
PloS one
|August 29, 2025
Resumen
El cilostazol y el sildenafil, inhibidores de la fosfodiesterasa, no impidieron la aortopatía torácica en un modelo de ratón. Estos fármacos no afectaron la formación ni la ruptura de aneurismas en ratones tratados con β-aminopropionitril (BAPN).
Área de la Ciencia:
- Investigación cardiovascular
- Farmacología
- Medicina traslacional
Sus antecedentes:
- Las aortopatías torácicas, incluidos el aneurisma y la disección, son enfermedades vasculares críticas.
- El cilostazol (inhibidor de la PDE3) y el sildenafil (inhibidor de la PDE5) son prometedores en los modelos de aneurisma aórtico abdominal.
- Su eficacia en la aortopatía torácica sigue siendo inexplorada.
Objetivo del estudio:
- Investigar los efectos del cilostazol y el sildenafil en un modelo de ratón de aortopatía torácica.
- Determinar si estos inhibidores de la fosfodiesterasa pueden prevenir o mitigar la progresión de la enfermedad.
Principales métodos:
- Inducción de la aortopatía torácica en ratones mediante el uso de β-aminopropionitril (BAPN).
- La administración de cilostazol o sildenafil a través de una dieta suplementaria.
- Confirmación de la presencia del fármaco mediante espectrometría de masas.
- Evaluación de la ruptura aórtica y la formación de aneurismas.
Principales resultados:
- BAPN aumentó la expresión de los genes Pde3a y Pde5a en la aorta.
- Los tratamientos farmacológicos confirmaron las concentraciones plasmáticas adecuadas.
- Ni el cilostazol ni el sildenafil alteraron la ruptura aórtica inducida por BAPN o el desarrollo de aneurismas.
Conclusiones:
- El cilostazol y el sildenafil no parecen influir en el desarrollo o la progresión de la aortopatía torácica inducida por BAPN en ratones.
- Se necesitan más investigaciones para explorar estrategias terapéuticas alternativas para las enfermedades de la aorta torácica.
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