Adenovirus-mediated gene transfer of urokinase plasminogen inhibitor inhibits angiogenesis in experimental arthritis.
Gene Ther
; 9(3): 192-200, 2002 Feb.
Article
en En
| MEDLINE
| ID: mdl-11859422
Plasmin is essential for metalloproteases activation, endothelial cell migration and degradation of the extracellular matrix. The process is common to neoangiogenesis pannus formation and cartilage degradation within arthritic joints. Since 80% of synovial cells express urokinase plasminogen activator receptor (uPAR), we investigated the inhibition of plasmin activation in a collagen-induced arthritis (CIA) mice model, by expressing a uPA/uPAR antagonist molecule (ATF) fused to human serum albumin (HSA) to extend its serum half-life. Overexpression was obtained with an adenoviral vector expressing the chimeric murine ATF-HSA. We showed that the genetic coupling did not significantly reduce the ability of the ATF moiety to interact with its receptor uPAR. The chimeric protein was detectable in the sera of injected mice 7 days following Ad-mATF-HSA injection, then decreased in parallel with the anti-HSA titer increase. Systemic Ad-mATF-HSA injection performed on day 25 following CIA induction decreased the incidence of arthritis and the severity of the disease. Moreover, synovial angiogenesis in arthritic paws was decreased after Ad-mATF-HSA gene transfer, as assessed by smooth muscle actin immunostaining. The preventive effect observed on arthritis was related to the decrease in angiogenesis, rather than inhibition of extracellular matrix degradation.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Artritis Experimental
/
Activador de Plasminógeno de Tipo Uroquinasa
/
Terapia Genética
/
Adenoviridae
/
Vectores Genéticos
/
Neovascularización Patológica
Límite:
Animals
Idioma:
En
Revista:
Gene Ther
Asunto de la revista:
GENETICA MEDICA
/
TERAPEUTICA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Francia
Pais de publicación:
Reino Unido