Adenovirus-mediated VEGF gene therapy enhances venous thrombus recanalization and resolution.

Modarai, B; Humphries, J; Burnand, K G; Gossage, J A; Waltham, M; Wadoodi, A; Kanaganayagam, G S; Afuwape, A; Paleolog, E; Smith, A

Modarai, B; Humphries, J; Burnand, K G; Gossage, J A; Waltham, M; Wadoodi, A; Kanaganayagam, G S; Afuwape, A; Paleolog, E; Smith, A.

Afiliación

Modarai B; Academic Department of Surgery, St Thomas' Hospital, North Wing, London, United Kingdom.

Arterioscler Thromb Vasc Biol ; 28(10): 1753-9, 2008 Oct.

Article en En | MEDLINE | ID: mdl-18669887

RESUMEN

OBJECTIVE: Rapid thrombus recanalization reduces the incidence of post-thrombotic complications. This study aimed to discover whether adenovirus-mediated transfection of the vascular endothelial growth factor gene (ad.VEGF) enhanced thrombus recanalization and resolution. METHODS AND RESULTS: In rats, thrombi were directly injected with either ad.VEGF (n=40) or ad.GFP (n=37). Thrombi in SCID mice (n=12) were injected with human macrophages transfected with ad.VEGF or ad.GFP. Thrombi were analyzed at 1 to 14 days. GFP was found mainly in the vein wall and adventitia by 3 days, but was predominantly found in cells within the body of thrombus by day 7. VEGF levels peaked at 4 days (376+/-299 pg/mg protein). Ad.VEGF treatment reduced thrombus size by >50% (47.7+/-5.1 mm(2) to 22.0+/-4.0 mm(2), P=0.0003) and increased recanalization by >3-fold (3.9+/-0.69% to 13.6+/-4.1%, P=0.024) compared with controls. Ad.VEGF treatment increased macrophage recruitment into the thrombus by more than 50% (P=0.002). Ad.VEGF-transfected macrophages reduced thrombus size by 30% compared with controls (12.3+/-0.89 mm(2) to 8.7+/-1.4 mm(2), P=0.04) and enhanced vein lumen recanalization (3.39+/-0.34% to 5.07+/-0.57%, P=0.02). CONCLUSIONS: Treatment with ad.VEGF enhanced thrombus recanalization and resolution, probably as a consequence of an increase in macrophage recruitment.

Asunto(s)

Adenoviridae/genética; Técnicas de Transferencia de Gen; Terapia Genética/métodos; Vectores Genéticos; Macrófagos/trasplante; Factor A de Crecimiento Endotelial Vascular/metabolismo; Trombosis de la Vena/terapia; Animales; Línea Celular; Modelos Animales de Enfermedad; Genes Reporteros; Proteínas Fluorescentes Verdes/metabolismo; Humanos; Macrófagos/metabolismo; Masculino; Ratones; Ratones SCID; Ratas; Ratas Wistar; Factores de Tiempo; Factor A de Crecimiento Endotelial Vascular/genética; Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo; Trombosis de la Vena/genética; Trombosis de la Vena/metabolismo; Trombosis de la Vena/patología

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia Genética / Adenoviridae / Técnicas de Transferencia de Gen / Trombosis de la Vena / Factor A de Crecimiento Endotelial Vascular / Vectores Genéticos / Macrófagos Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Arterioscler Thromb Vasc Biol Asunto de la revista: ANGIOLOGIA Año: 2008 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

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