Postprocedure administration of insulin in canine autologous vein grafting: a potential strategy to attenuate intimal hyperplasia.
J Cardiovasc Pharmacol
; 56(4): 402-12, 2010 Oct.
Article
en En
| MEDLINE
| ID: mdl-20625311
ABSTRACT
Intimal hyperplasia (IH) exerts a critical role in vein graft failure after arterial bypassing. Insulin has been demonstrated to remarkably decrease IH in the rat carotid injury model. We hypothesized that postoperative insulin medication prevents the autologous vein graft from IH. Dogs were subjected to jugular-carotid interposition bypass grafting and intravenously infused with vehicle, glucose-insulin-potassium, glucose-potassium, or glucose-insulin-potassium plus Wortmannin 5 minutes before and 4 hours after reperfusion. Then vein grafts were harvested for caspase-3 activation, cell apoptosis, phosphorylated Akt, and endothelial nitric oxide synthase level assays. Other dogs undergoing the same operation were administered with subcutaneous injection of 4 U insulin or 0.5 mL saline two times per day for 1 month postoperatively. Vein grafts were sampled to assess cell proliferation, intimal/medial thickness, and expression of endothelial nitric oxide synthase and [alpha]-smooth muscle actin. Glucose-potassium aggravated apoptosis and caspase-3 activation and decreased Akt and endothelial nitric oxide synthase phosphorylation; however, glucose-insulin-potassium significantly inhibited cell apoptosis and caspase-3 activation and increased phosphorylated Akt and pendothelial nitric oxide synthase levels in canine vein grafts. Wortmannin largely abolished the glucose-insulin-potassium-elicited effects. Moreover, postoperative insulin use greatly inhibited cell proliferation, reduced intimal/medial thickness, upregulated endothelial nitric oxide synthase, and [alpha]-smooth muscle actin expression. Insulin protects autologous vein grafts possibly through the phosphatidylinositol-3 kinase/Akt signaling pathway and prevents IH in autologous vein grafts.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Túnica Íntima
/
Arteria Carótida Común
/
Injerto Vascular
/
Hipoglucemiantes
/
Insulina
/
Venas Yugulares
Límite:
Animals
Idioma:
En
Revista:
J Cardiovasc Pharmacol
Año:
2010
Tipo del documento:
Article
País de afiliación:
China