Received for publication January 19, 2006.
Revised March 26, 2006.
Accepted for publication March 31, 2006.

Cilostazol Protects Diabetic Rats from Vascular Inflammation via NF-B-dependent Down-regulation of VCAM-1 Expression

Abstract

Vascular cell adhesion molecule (VCAM) -1 plays a critical role in the initiation and development of vascular inflammation and selective inhibition of adhesion molecules expressed by endothelial cells may present a new therapeutic strategy for the treatment of vascular complications associated with diabetes mellitus. Increasing evidence indicates that cilostazol, a cAMP phosphodiesterase inhibitor, reduces VCAM-1 expression on endothelial cells. In this study, we have tested the effect of cilostazol on the development of vascular inflammation in rats with STZ-induced diabetes and determined the mechanism by which cilostazol prevents diabetes-induced vascular inflammation in the aorta. Diabetic rats were treated with different dose of cilostazol (27 mg/kg/day or 9 mg/kg/day) for 8 weeks and aortae removed for the evaluation of vascular inflammation. The VCAM-1 protein expression and VCAM-1 mRNA transcripts were analyzed by immounhistochemical staining and in situ hybridization assay respectively. Our results demonstrated that cilostazol treatment prevents the over-expression of VCAM-1 and protects diabetic rats from vascular inflammation. More importantly, our mechanistic studies suggested that cilostazol controls the VCAM-1 over-expression via inhibiting the activation of nuclear factor (NF) -B.

Key words: NF-B, VCAM-1, cilostazol, diabetes, inflammation, vascular complications