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La terapia dirigida con MicroRNA-145 reduce la aterosclerosis
Fina Lovren1, Yi Pan, Adrian Quan
1Division of Cardiac Surgery, Li Ka Shing Knowledge Institute at St. Michael's Hospital, Toronto, Ontario, Canada.
Circulation
|September 12, 2012
Resumen
La terapia génica MicroRNA-145 en ratones redujo el tamaño de la placa aterosclerótica y promovió la estabilidad de la placa. Esto sugiere que el microRNA-145 es un objetivo terapéutico potencial para las enfermedades cardiovasculares.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- La medicina molecular es una medicina molecular.
- Terapia génica Terapia génica La terapia génica es una terapia genética.
Sus antecedentes:
- Los microARN son reguladores clave de la expresión génica involucrada en las enfermedades crónicas.
- MicroRNA-145 (miR-145) está altamente expresado en las células del músculo liso vascular (VSMC) e influye en su destino.
- El papel de miR-145 en la aterosclerosis y la estabilidad de la placa requiere más investigación.
Objetivo del estudio:
- Investigar el potencial terapéutico del microARN-145 (miR-145) en la modulación de la aterosclerosis.
- Para determinar si la sobreexpresión específica de VSMC de miR-145 tiene un impacto en el desarrollo de la placa aterosclerótica y la estabilidad in vivo.
Principales métodos:
- Los ratones knockout de Apolipoproteína E (ApoE(-/-)) fueron tratados con un lentivirus que expresaba miR-145 bajo un promotor específico de VSMC (SM22α) o un lentivirus de control.
- Los ratones fueron alimentados con una dieta occidental durante 12 semanas para inducir la aterosclerosis.
- Las lesiones ateroscleróticas se analizaron para el tamaño de la placa, la morfología, la composición celular y los marcadores de fenotipo VSMC.
Principales resultados:
- La administración de miR-145 dirigida a SMC redujo significativamente el tamaño de la placa aterosclerótica en las arterias principales.
- El tratamiento aumentó el área de la tapa fibrosa, el contenido de colágeno y los marcadores VSMC (calponina, actina del músculo liso α), mientras que disminuyó el área del núcleo necrótico y la infiltración de macrófagos.
- La sobreexpresión de miR-145 redujo el KLF4 y aumentó la expresión de miocardina, promoviendo un fenotipo VSMC contráctil.
Conclusiones:
- La sobreexpresión específica del VSMC de miR-145 es una nueva estrategia terapéutica para limitar la progresión de la placa aterosclerótica.
- Este enfoque modifica efectivamente la morfología de la placa y la composición celular, mejorando la estabilidad y reduciendo el riesgo de ruptura.
- miR-145 es prometedor como objetivo para el tratamiento de la aterosclerosis y la prevención de la ruptura de la placa.
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