Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression.
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.
Gao
Ling
L
Center of Scientific Research, and Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Jinan, Shandong 250021, China, and Department of Neurology, Case Western Reserve University, Cleveland, OH, USA.
Wang
Furong
F
Wang
Bo
B
Gong
Bendi
B
Zhang
Jie
J
Zhang
Xiumei
X
Zhao
Jiajun
J
D000818:Animals; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D014652:Vascular Diseases / Q000378:metabolism / Q000517:prevention & control*
D016328:NF-kappa B; D013777:Tetrazoles; D019010:Vascular Cell Adhesion Molecule-1; D000077407:Cilostazol