Nonviral monocyte chemoattractant protein-1 gene transfer improves arteriogenesis after femoral artery occlusion.
Gene Ther
; 11(23): 1685-93, 2004 Dec.
Article
en En
| MEDLINE
| ID: mdl-15470479
ABSTRACT
Local infusion of recombinant monocyte chemoattractant protein-1 (MCP-1) has been shown to enhance collateral artery formation in rabbit and pig hindlimb models. Owing to clinical disadvantages of protein infusion, a nonviral, liposome-based MCP-1 gene transfer was developed. Collateralization in a porcine hindlimb model served to provide a proof-of-principle for the functional benefit of MCP-1 overexpression. Development of arterial conductance as a measure of functionally relevant collateralization was evaluated in occluded as well as untreated hindlimbs in each animal. At the time of occlusion, MCP-1 and control DNA/DC-30 lipoplexes were transferred to femoral arteries of Goettingen minipigs (two therapeutic MCP-1 groups 2 and 4 microg and one control group), using the Infiltrator local drug-delivery device. At 2 weeks following occlusion, collateralization was determined as changes in peripheral haemodynamic conductance, peripheral over aortic blood pressure ratio and angiographically visible morphology of the peripheral vessel tree. Nonviral MCP-1 gene transfer significantly improved peripheral conductance (control 11.69+/-2.78%, 2 microg 23.81+/-2.81%, P<0.05 and 4 microg 23.36+/-3.1%, P<0.05; n=12 per group) as well as the ratio of peripheral over aortic blood pressure (control 0.64+/-0.03%, 2 microg 0.75+/-0.02%, P<0.05 and 4 mug 0.75+/-0.02%, P<0.05; n=12 per group) when compared to the untreated controls 2 weeks after occlusion. Thus, it could be demonstrated for the first time that in situ overexpression of MCP-1 following local nonviral gene transfer is a potential approach to improve peripheral collateralization.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Arteriopatías Oclusivas
/
Terapia Genética
/
Enfermedades Vasculares Periféricas
/
Circulación Colateral
/
Quimiocina CCL2
/
Arteria Femoral
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2004
Tipo del documento:
Article
País de afiliación:
Alemania