Gene transfer in utero biologically engineers a patent ductus arteriosus in lambs by arresting fibronectin-dependent neointimal formation.
Nat Med
; 5(2): 176-82, 1999 Feb.
Article
em En
| MEDLINE
| ID: mdl-9930865
ABSTRACT
Closure of the ductus arteriosus requires prenatal formation of intimal cushions, which occlude the vessel lumen at birth. Survival of newborns with severe congenital heart defects, however, depends on ductal patency. We used a gene transfer approach to create a patent ductus arteriosus by targeting the fibronectin-dependent smooth muscle cell migration required for intimal cushion formation. Fetal lamb ductus arteriosus was transfected in utero with hemagglutinating virus of Japan liposomes containing plasmid encoding 'decoy' RNA to sequester the fibronectin mRNA binding protein. Fibronectin translation was inhibited and intimal cushion formation was prevented. We thus established the essential role of fibronectin-dependent smooth muscle cell migration in intimal cushion formation in the intact animal and the feasibility of incorporating biological engineering in the management of congenital heart disease.
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Base de dados:
MEDLINE
Assunto principal:
Transfecção
/
Terapia Genética
/
Fibronectinas
/
Permeabilidade do Canal Arterial
Limite:
Animals
/
Pregnancy
Idioma:
En
Ano de publicação:
1999
Tipo de documento:
Article