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La timosina beta4 es un factor paracrino esencial de la cardioprotección mediada por células progenitoras
Rabea Hinkel1, Chiraz El-Aouni, Tonia Olson
1Medizinische Klinik I, University Clinic Grosshadern, Munich, Germany.
Circulation
|April 23, 2008
Resumen
La timosina beta4 (Tbeta4) media los efectos cardioprotectores de las células progenitoras endoteliales embrionarias (eEPC) después de la isquemia miocárdica. Tbeta4 solo imita los beneficios de eEPC, reduciendo el tamaño del infarto y mejorando la función cardíaca.
Área de la Ciencia:
- Biología Cardiovascular Biología Cardiovascular
- La Medicina Regenerativa es una Medicina Regenerativa.
- Terapia Celular Terapia celular es una terapia celular que se utiliza para tratar el cáncer.
Sus antecedentes:
- La isquemia miocárdica prolongada conduce a la pérdida de cardiomiocitos, incluso después de la revascularización.
- Las células progenitoras endoteliales embrionarias (eEPC) ofrecen protección paracrina contra la lesión por isquemia-reperfusión.
- El papel de la timosina beta4 (Tbeta4) en la cardioprotección mediada por eEPC requiere investigación.
Objetivo del estudio:
- Para determinar si la timosina beta4 (Tbeta4) media los efectos cardioprotectores de las células progenitoras endoteliales embrionarias (eEPC).
Principales métodos:
- In vitro: cardiomiocitos neonatales de rata sometidos a hipoxia-reoxigenación con/sin eEPC o ARN de horquilla corta Tbeta4 (shRNA).
- In vivo: Los cerdos se sometieron a una oclusión de la arteria coronaria; retroinfusión de eEPCs, Tbeta4 shRNA transfected eEPCs, o Tbeta4 solo.
- Evaluación del tamaño del infarto, la función cardíaca (acortamiento endocárdico) y la inflamación (actividad de la mieloperoxidasa).
Principales resultados:
- Los eEPC aumentaron significativamente la supervivencia de los cardiomiocitos in vitro y redujeron el tamaño del infarto in vivo.
- El knockdown de Tbeta4 abolió la cardioprotección mediada por eEPC, mientras que la administración de Tbeta4 imitaba los efectos de eEPC.
- La administración de Tbeta4 redujo el tamaño del infarto y mejoró la función cardíaca, comparable a los eEPC.
Conclusiones:
- La timosina beta4 (Tbeta4) juega un papel crucial en la cardioprotección a corto plazo proporcionada por las células progenitoras endoteliales embrionarias (eEPC).
- La administración de Tbeta4 por sí sola puede replicar los efectos beneficiosos de los eEPC en la mitigación de la lesión por isquemia-reperfusión.
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