Ribozyme-mediated inhibition of rat leukocyte-type 12-lipoxygenase prevents intimal hyperplasia in balloon-injured rat carotid arteries.
Circulation
; 103(10): 1446-52, 2001 Mar 13.
Article
em En
| MEDLINE
| ID: mdl-11245651
ABSTRACT
BACKGROUND:
12-Lipoxygenase (12-LO) products of arachidonate metabolism have growth and chemotactic effects in vascular smooth muscle cells. We have also recently demonstrated increased 12-LO mRNA and protein expression in the neointima of balloon-injured rat carotid arteries. In this study, we evaluated whether 12-LO activation plays a role in neointimal thickening in this rat model by using a specific ribozyme (Rz) directed to rat 12-LO. METHODS ANDRESULTS:
We designed a chimeric DNA-RNA hammerhead Rz to cleave rat leukocyte-type 12-LO mRNA. This Rz dose-dependently cleaved a 166-nucleotide target 12-LO mRNA substrate in vitro and reduced 12-LO mRNA and protein expression in rat vascular smooth muscle cells. A control mutant Rz (MRz) with a point mutation in the catalytic site was inactive. To test the in vivo efficacy of the 12-LO Rz, the left common carotid arteries of rats were injured with a balloon catheter. The distal half of the injured arteries was treated with Rz or MRz mixed with lipofectin. The proximal half received only lipofectin. Twelve days after injury, intima-to-media ratios were significantly lower in the Rz-treated sections than in untreated sections from the same rat (0.742+/-0.16 versus 1.749+/-0.12, P<0.001). In contrast, the MRz had no significant effect.CONCLUSIONS:
These results indicate the important role of the leukocyte-type 12-LO pathway in restenosis in response to injury.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Araquidonato 12-Lipoxigenase
/
Doenças das Artérias Carótidas
/
RNA Catalítico
/
Túnica Íntima
/
Leucócitos
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos