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Entrega de genes VEGF al miocardio: efectos perjudiciales de la expresión no regulada

R J Lee¹, M L Springer, W E Blanco-Bose

¹Department of Medicine and the Cardiovascular Research Institute, University of California, San Francisco, USA. lee@ep4.ucsf.edu

|August 23, 2000

Resumen

La expresión continua del factor de crecimiento endotelial vascular (VEGF) a través de la administración de mioblastos en ratones condujo a una mortalidad significativa y al desarrollo de tumores vasculares. Esto pone de relieve la necesidad crítica de un suministro controlado de VEGF en la angiogénesis terapéutica.

Área de la Ciencia:

Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular Investigación cardiovascular
Terapia génica Terapia génica La terapia génica es una terapia genética.
La Medicina Regenerativa es una Medicina Regenerativa.

Sus antecedentes:

El factor de crecimiento endotelial vascular (VEGF) se explora para la angiogénesis terapéutica en afecciones cardíacas isquémicas.
La investigación actual se centra principalmente en los sistemas de entrega transitorios para el VEGF.
Este estudio investiga la expresión continua de VEGF utilizando el suministro mediado por mioblastos.

Objetivo del estudio:

Para evaluar los efectos de la expresión continua de VEGF en el miocardio.
Evaluar la seguridad y eficacia de la administración de VEGF mediada por mioblastos.

Principales métodos:

Los mioblastos murinos diseñados para expresar VEGF y beta-galactosidasa fueron implantados en ratones inmunodeficientes.
Los ratones de control recibieron mioblastos que expresan sólo beta-galactosidasa.
Los corazones fueron analizados histológicamente y vía inmunohistoquímica.

Principales resultados:

La expresión continua de VEGF se tradujo en un fracaso para prosperar y la mortalidad en el grupo experimental.
La histología reveló tumores vasculares intramurales que se asemejan a hemangiomas en el sitio de implantación.
Los marcadores de células endoteliales (eNOS, CD31) fueron abundantes en las lesiones observadas.

Conclusiones:

La expresión continua y no regulada de VEGF está relacionada con resultados adversos, incluida la muerte y la formación de tumores.
Estos hallazgos enfatizan la necesidad de regular la expresión de VEGF para una angiogénesis terapéutica segura.
La administración de VEGF mediada por mioblastos requiere un control cuidadoso para evitar efectos perjudiciales.

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