Catalytic oligodeoxynucleotides define a key regulatory role for early growth response factor-1 in the porcine model of coronary in-stent restenosis.
Circ Res
; 89(8): 670-7, 2001 Oct 12.
Article
en En
| MEDLINE
| ID: mdl-11597989
ABSTRACT
Early growth response factor-1 (Egr-1) controls the expression of a growing number of genes involved in the pathogenesis of atherosclerosis and postangioplasty restenosis. Egr-1 is activated by diverse proatherogenic stimuli. As such, this transcription factor represents a key molecular target in efforts to control vascular lesion formation in humans. In this study, we have generated DNAzymes targeting specific sequences in human EGR-1 mRNA. These molecules cleave in vitro transcribed EGR-1 mRNA efficiently at preselected sites, inhibit EGR-1 protein expression in human aortic smooth muscle cells, block serum-inducible cell proliferation, and abrogate cellular regrowth after mechanical injury in vitro. These DNAzymes also selectively inhibit EGR-1 expression and proliferation of porcine arterial smooth muscle cells and reduce intimal thickening after stenting pig coronary arteries in vivo. These findings demonstrate that endoluminally delivered DNAzymes targeting EGR-1 may serve as inhibitors of in-stent restenosis.
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Bases de datos:
MEDLINE
Asunto principal:
Factores de Transcripción
/
Proteínas Inmediatas-Precoces
/
Vasos Coronarios
/
ADN Catalítico
/
Proteínas de Unión al ADN
/
Oclusión de Injerto Vascular
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Circ Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Australia