Blockade of TGF-beta by Catheter-based Gene Transfer of a Soluble TGF-beta Type II Receptor Inhibits Neointima Formed after Stenting
Korean Circulation Journal
;
: 59-68, 2004.
Artículo
en Inglés
| WPRIM
| ID: wpr-82007
ABSTRACT
BACKGROUND:
Enhanced extracellular matrix (ECM) accumulation is an important finding in coronary stent restenotic tissue, in which TGF-beta, implicated in ECM formation, is expressed abundantly. We assessed the hypothesis that blockade of TGF-beta by the local delivery of an adenovirus expressing a soluble form of the TGF-beta type II receptor (AdT beta-ExR), inhibits stent-induced neointima in porcine coronary arteries.METHODS:
Two remote coronary arterial segments (n=20) per pig randomly received 1x10(9) pfu of either AdT beta-ExR or adenovirus expressing beta-galactosidase (AdLacZ)/PBS, using an Infiltrator(TM). Stents (n=20) were deployed, after gene transfer, in each segment of 10 pigs. Localized transgene expression was confirmed by both reverse transcription-PCR and immunohistochemistry. Computer-based morphometric assessment was performed in the stented arteries 4 weeks after the gene transfer.RESULTS:
There was significantly less intimal area (1.57+/-0.49 vs. 2.13+/-0.34 mm2), area ratio of intima/media (0.84+/-0.44 vs. 1.32+/-0.48) and higher neointimal cell density (3121+/-330 vs. 2812+/-183 cells/mm2) in the arteries treated with AdT beta-ExR compared to the controls (all, p<0.05). Neither the cell proliferation rate, assessed by PCNA immunohistochemistry, nor the injury score were significantly different between the two groups. The distribution of hyaluronan in the intima was less in 4 of the 6 AdT beta-ExR treated arteries compared to the controls.CONCLUSION:
Blockade of TGF-beta, by a local in vivo gene transfer of a soluble TGF-beta receptor, inhibits stent-induced neointima, probably by inhibiting the ECM accumulation in porcine coronary arteries, which may have therapeutic potential in the inhibition of restenosis after stenting.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Arterias
/
Porcinos
/
Inmunohistoquímica
/
Terapia Genética
/
Recuento de Células
/
Stents
/
Adenoviridae
/
Factor de Crecimiento Transformador beta
/
Beta-Galactosidasa
/
Receptores de Factores de Crecimiento Transformadores beta
Idioma:
Inglés
Revista:
Korean Circulation Journal
Año:
2004
Tipo del documento:
Artículo
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