Bortezomib Reduces Neointimal Hyperplasia in a Rat Carotid Artery Injury Model
Korean Circulation Journal
;
: 592-599, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-78988
ABSTRACT
BACKGROUND AND OBJECTIVES:
The ubiquitin-proteasome system is the major intracellular protein degradation pathway in the eukaryotic cells. Bortezomib inhibits 26S proteasome-induced I-kappaBalpha degradation and suppresses nuclear factor-kappa B (NF-kappaB) activation. We examined the effect of bortezomib on neointima formation after of a rat carotid artery balloon injury. MATERIALS ANDMETHODS:
After carotid artery balloon denudation, bortezomib was immediately administered by tail vein injection (systemic treatment) and by using an F-127 pluronic gel (perivascular treatment). Two weeks after the injury, we compared the degree of neointima formation in the carotid artery and the tissue expression patterns of NF-kappaB and I-kappaBalpha.RESULTS:
The systemic treatment group exhibited a 29% reduction in neointima volume at two weeks after the balloon injury. On the western blot analysis, the bortezomib group exhibited an increased I-kappaBalpha expression, which suggested the inhibition of I-kappaBalpha degradation. On immunofluorescence analysis, the nuclear import of NF-kappaB was clearly decreased in the systemic bortezomib group. The perivascular bortezomib treatment group exhibited a significant reduction in the neointimal area (0.21+/-0.06 mm2 vs. 0.06+/-0.01 mm2, p<0.05), the neointima/media area ratio (1.43+/-0.72 vs. 0.47+/-0.16, p<0.05) and the % area stenosis (45.5+/-0.72% vs. 14.5+/-0.05%, p<0.05) compared with the control group. In situ vascular smooth muscle cell proliferation at 2 days after the injury was significantly inhibited (24.7+/-10.9% vs. 10.7+/-4.7%, p<0.05).CONCLUSION:
Bortezomib suppressed NF-kappaB activation through the inhibition of I-kappaBalpha degradation, and significantly reduced neointima formation in a rat carotid artery injury model. These data suggested that bortezomib represented a new potent therapeutic agent for the prevention of restenosis.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Pirazinas
/
Veias
/
Ácidos Borônicos
/
Artérias Carótidas
/
Western Blotting
/
NF-kappa B
/
Imunofluorescência
/
Angioplastia
/
Constrição Patológica
/
Lesões das Artérias Carótidas
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
Korean Circulation Journal
Ano de publicação:
2013
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS