http://jpet.aspetjournals.org/cgi/content/abstract/318/1/53Journal of Pharmacology And Experimental Therapeutics
First published on April 4, 2006; DOI: 10.1124/jpet.106.101444
ENDOCRINE AND DIABETES
Cilostazol Protects Diabetic Rats from Vascular Inflammation via Nuclear Factor-{kappa}B-Dependent Down-Regulation of Vascular Cell Adhesion Molecule-1 Expression
Ling Gao, Furong Wang, Bo Wang, Bendi Gong, Jie Zhang, Xiumei Zhang, and Jiajun Zhao
Center of Scientific Research (L.G., F.W., Jie.Z.) and Department of Endocrinology and Metabolism (Jia.Z.), Shandong Provincial Hospital, Shandong, China; Diabetes Research Center, Division of Pediatric Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio (B.W.); Department of Neurology, Case Western Reserve University, Cleveland, Ohio (B.G.); and Department of Pharmacology, Medical School, Shandong University, Jinan, Shandong, China (X.Z.)
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-{kappa}B.
