Antisense Bcl-x oligonucleotide induces apoptosis and prevents arterial neointimal formation in murine cardiac allografts.
Cardiovasc Res
; 45(3): 783-7, 2000 Feb.
Article
em En
| MEDLINE
| ID: mdl-10728401
ABSTRACT
OBJECTIVE:
Cardiac allograft arteriosclerosis, which limits long-term survival of recipients, cannot be prevented by conservative therapies. The arteriopathy is characterized by diffuse intimal thickening comprised of proliferative smooth muscle cells (SMCs). Cell death is a prominent feature of atherosclerosis; Bcl-x is one of the anti-apoptotic mediators.METHODS:
To test the hypothesis that antisense bcl-x oligodeoxynucleotide (ODN) is effective in preventing intimal hyperplasia through enhancing apoptosis after cardiac transplantation, we performed single intraluminal delivery of antisense bcl-x ODN into murine cardiac allografts (n = 9). DBA/2 (H-2d) hearts were transplanted into B10.D2 (H-2d) mice. Sense bcl-x ODN (n = 8) and no treatment (n = 8) studies were also performed.RESULTS:
Allografts were harvested at 4 weeks after transplantation; all allografts kept beating throughout the period. Coronary intimal thickening had developed in nontreated and sense ODN transfected allografts at 4 weeks after transplantation with enhanced expression of Bcl-x and cell adhesion molecules, and suppressed apoptosis. However, antisense bcl-x ODN prevented neointimal formation through enhanced apoptosis.CONCLUSION:
These results indicate that apoptosis of vascular SMCs induced by Bcl-x is associated with initial hyperplasia after heart transplantation. Antisense bcl-x ODN inhibits SMC proliferation by inducing apoptosis in graft coronary arteries.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Arteriosclerose
/
Oligonucleotídeos Antissenso
/
Túnica Íntima
/
Apoptose
/
Técnicas de Transferência de Genes
/
Proteínas Proto-Oncogênicas c-bcl-2
Limite:
Animals
Idioma:
En
Revista:
Cardiovasc Res
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Japão