RT Journal Article
SR Electronic
T1 Cilostazol Protects Diabetic Rats from Vascular Inflammation via Nuclear Factor-κB-Dependent Down-Regulation of Vascular Cell Adhesion Molecule-1 Expression
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 53
OP 58
DO 10.1124/jpet.106.101444
VO 318
IS 1
A1 Ling Gao
A1 Furong Wang
A1 Bo Wang
A1 Bendi Gong
A1 Jie Zhang
A1 Xiumei Zhang
A1 Jiajun Zhao
YR 2006
UL http://jpet.aspetjournals.org/content/318/1/53.abstract
AB 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 streptozotocin-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 or 9 mg/kg/day) for 8 weeks, and aortae were removed for the evaluation of vascular inflammation. The VCAM-1 protein expression and VCAM-1 mRNA transcripts were analyzed by immunohistochemical staining and in situ hybridization assay, respectively. Our results demonstrated that cilostazol treatment prevents the overexpression of VCAM-1 and protects diabetic rats from vascular inflammation. More importantly, our mechanistic studies suggested that cilostazol controls the VCAM-1 overexpression via inhibiting the activation of nuclear factor-κB. The American Society for Pharmacology and Experimental Therapeutics