Alagebrium Chloride, a Novel Advanced Glycation End-Product Cross Linkage Breaker, Inhibits Neointimal Proliferation in a Diabetic Rat Carotid Balloon Injury Model
Korean Circulation Journal
;
: 520-526, 2010.
Artigo
em Inglês
| WPRIM
| ID: wpr-23760
ABSTRACT
BACKGROUND AND OBJECTIVES:
Vascular perturbation induced by advanced glycation end-products (AGEs) leads to progression of atherosclerosis, plaque instability, and vascular inflammation, which results in a higher risk of neointimal proliferation. Here we investigated the inhibitory effect of alagebrium chloride (ALT-711), a breaker of AGE-based cross links, on neointimal proliferation in a carotid artery balloon injury model in diabetic rats induced by streptozotocin (STZ). MATERIALS ANDMETHODS:
Rat aortic vascular smooth muscle cells (RASMCs) were treated with 1-100 microM of alagebrium added 24 hours before the addition of AGEs. This in vivo study was done using 8-week-old male rats that were injected intraperitoneally with 80 mg/kg STZ. Sixteen weeks later, the diabetic rats were treated with 10 mg/kg alagebrium for 4 weeks, after which carotid artery balloon injury was induced. After 4 weeks, the animals were sacrificed for histological analysis.RESULTS:
Proliferation of RASMCs was significantly inhibited in alagebrium-treated cells. Alagebrium dose-dependently inhibited AGE-mediated formation of reactive oxygen species (ROS), extracellular signal-regulated kinase phosphorylation, and cyclooxygenase-2 expression. The cellular mechanisms of AGE-induced connective tissue and extracellular matrix expression were decreased in the alagebrium-treated group. This in vivo study shows that expression of AGE receptors and neointima hyperplasia are significantly suppressed in balloon-injured rats treated with alagebrium.CONCLUSION:
Alagebrium treatment in diabetic rats significantly inhibits neointimal hyperplasia after carotid balloon injury due to its inhibition of intracellular ROS synthesis, which results in inhibition of RASMCs proliferation.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Fosforilação
/
Fosfotransferases
/
Tiazóis
/
Artérias Carótidas
/
Espécies Reativas de Oxigênio
/
Estreptozocina
/
Tecido Conjuntivo
/
Aterosclerose
/
Ciclo-Oxigenase 2
/
Matriz Extracelular
Limite:
Animais
/
Humanos
/
Masculino
Idioma:
Inglês
Revista:
Korean Circulation Journal
Ano de publicação:
2010
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS