Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression.
作者
Gao Ling;Wang Furong;Wang Bo;Gong Bendi;Zhang Jie;Zhang Xiumei;Zhao Jiaju
作者单位
摘要
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-kappaB.
关键词
Animals|Diabetes Mellitus, Experimental/drug therapy/metabolism|Down-Regulation/drug effects/physiology|Endothelium, Vascular/drug effects/metabolism|Gene Expression Regulation/drug effects/physiology|Male|NF-kappa B/antagonists & inhibitors/metabolism|Rats|Rats, Sprague-Dawley|Tetrazoles/pharmacology/therapeutic use|Vascular Cell Adhesion Molecule-1/biosynthesis|Vascular Diseases/metabolism/prevention & contro
基本信息
