Effect of hyperlipidemia on endothelial VCAM-1 expression and the protective role of fenofibrate

Abstract

The effect of hyperlipidemia and inflammation on endothelial functions was studied. The enrolled included control (basic chow), hyperlipidemia and fenofibrate-treated groups (high fat diet). The hyperlipidemia model was set up by four-week atherogenic diet, followed by a 16-week treatment in the fenofibrate-treated group (fenofibrate 40 mg/kg every day) and without treatment in the hyperlipidemia group, respectively. In the 20th week, serum lipid level and NO levels were measured, and the expression of vascular cell adhesion molecule-1 (VCAM-1) and cell adhesiveness in aortic endothelia observed by computer-aided system. Compared with the control group, hyperlipidemia rats showed lower levels of NO and increases in leukocyte accumulation on the endothelial surface, also stronger and more extensive endothelial expression of VCAM-1. In fenofibrate-treated group, the expression of VCAM-1 and leukocyte accumulation on the endothelial surface was decreased, while serum levels of NO were increased as compared with hyperlipidemia group. Hyperlipidemia can inhibit the NO activity and promote the damage of VACA-1 to aortic endothelia. Fenofibrate can effectively prevent the pathogenesis of atherosclerosis by restoring NO levels and down-regulating the VCAM-1 expression.