Antisense to transforming growth factor-beta(1) facilitates the apoptosis of macrophages in rat vein grafts.
J Vasc Res
; 45(5): 365-74, 2008.
Article
em En
| MEDLINE
| ID: mdl-18354256
ABSTRACT
BACKGROUND:
The success of peripheral vein grafts is limited by intimal hyperplasia. Transforming growth factor (TGF)-beta(1) has effects on cell proliferation, apoptosis and extracellular matrix synthesis. We have previously observed positive changes in vessel healing with antisense to TGF-beta(1).METHODS:
Adenovirus was used to transduce rat femoral artery vein grafts with antisense to TGF-beta(1) (Ad-AST) or the sequence encoding the bioactive form of TGF-beta(1) (Ad-BAT). Grafts were harvested at 1, 2, 4 and 12 weeks and formalin fixed for immunohistochemical studies of the cell markers proliferating cellular nuclear antigen (proliferation) and active caspase 3 (apoptosis). In situ DNA fragmentation assays were also performed to confirm active caspase 3 results.RESULTS:
Ad-AST treatment significantly (p = 0.05) increased apoptosis of macrophages inside the internal elastic lamina. In addition, Ad-AST treatment significantly increased the cellularity of the graft at early time points and reduced it at later time points (p = 0.01).CONCLUSION:
The low levels of TGF-beta(1) in Ad-AST treatment promote apoptosis of macrophages and provide an environment that is more conducive to the proliferation or infiltration of cells that contribute to healthy vessels.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Veias
/
Terapia Genética
/
Oligonucleotídeos Antissenso
/
Apoptose
/
Fator de Crescimento Transformador beta1
/
Artéria Femoral
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Oclusão de Enxerto Vascular
/
Macrófagos
Limite:
Animals
Idioma:
En
Revista:
J Vasc Res
Ano de publicação:
2008
Tipo de documento:
Article