Adenovirus-mediated gene transfer of a secreted transforming growth factor-beta type II receptor inhibits luminal loss and constrictive remodeling after coronary angioplasty and enhances adventitial collagen deposition.
Circulation
; 104(21): 2595-601, 2001 Nov 20.
Article
em En
| MEDLINE
| ID: mdl-11714656
ABSTRACT
BACKGROUND:
Extracellular matrix (ECM) remodeling is central to the development of restenosis after coronary angioplasty (PTCA). As a regulator of ECM deposition by vascular cells, substantial evidence implicates transforming growth factor-beta1 (TGF-beta1) in the pathogenesis of restenosis. We investigated the effects of intracoronary expression of a transgenic antagonist of TGF-beta1 on luminal loss after PTCA. METHODS ANDRESULTS:
Porcine coronary arteries were randomized to receive a recombinant adenovirus expressing a secreted form of TGF-beta type II receptor (Ad5-RIIs), an adenovirus expressing beta-galactosidase (Ad5-lacZ), or vehicle only by intramural injection at the site of PTCA. Computerized morphometry 28 days after angioplasty revealed a greater minimum luminal area in Ad5-RIIs-injected arteries (1.71+/-0.12 mm(2)) than in the Ad5-lacZ (1.33+/-0.13 mm(2)) or vehicle-only (1.08+/-0.17 mm(2); P=0.010 by ANOVA) groups. This was accompanied by greater areas within the internal (P=0.013) and external (P=0.031) elastic laminae in Ad5-RIIs-treated vessels. Adventitial collagen content at the site of injury was increased in the Ad5-RIIs group, in contrast to decreases in the Ad5-lacZ and vehicle-only groups (P=0.004).CONCLUSIONS:
Adenovirus-mediated antagonism of TGF-beta1 at the site of PTCA reduces luminal loss after PTCA by inhibiting constrictive remodeling. Antagonism of TGF-beta1 stimulates the formation of a dense collagenous adventitia, which prevents constrictive remodeling by acting as an external scaffold. These findings demonstrate the potential of gene therapy-mediated antagonism of TGF-beta1 as prophylactic therapy for restenosis.
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Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
/
Angioplastia Coronária com Balão
/
Adenoviridae
/
Colágeno
/
Receptores de Fatores de Crescimento Transformadores beta
/
Reestenose Coronária
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article