[Impact of fenofibrate on NO and endothelial VCAM-1 expression in hyperlipidemic rats].
OBJECTIVE
To investigate the mechanism of hyperlipidemia- and imflammation-induced functional impairment of the endothelium.


METHODS
The experiment was conducted using 3 groups of rats fed for 20 weeks with standard chow (control group), high-fat diet and high-fat diet with daily fenofibrate treatment (10 mg/kg, starting since the fifth week), respectively. After 4 and 20 weeks of feeding, respectively, serum lipid level and NO concentration were measured in the rats, and the epithelial vascular cell adhesion molecule-1 (VCAM-1) expression and cell adhesiveness to the aortic endothelium were observed.


RESULTS
Compared with the control group, the rats with hyperlipidemia induced by long-term high-fat diet feeding showed lower NO concentration and increased leukocyte accumulation on the endothelial surface, exhibiting also stronger and more extensive endothelial expression of VCAM-1. In contrast, the hyperlipidemic rats with fenofibrate treatment shoed significantly decreased VCAM-1 expression and leukocyte adhesion with recovery of the NO level.


CONCLUSIONS
NO deficiency and activation of inflammation are involved in vascular impairment in rats with high-fat diet-induced hyperlipidemia, and fenofibrate can effectively prevent atherosclerosis by restoring NO concentration and down-regulating VCAM-1 expression in these rats.
Wu
Jun
J
Department of Cardiology, First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510120, China. dr.wu@tom.com
Sun
Ming
M
Lin
Jin-chao
JC
He
Zhao-chu
ZC
Ou
Bi-ru
BR
Guo
Hai-sen
HS
D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control; D002448:Cell Adhesion; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D007249:Inflammation; D007962:Leukocytes / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D019010:Vascular Cell Adhesion Molecule-1; D009569:Nitric Oxide; D011345:Fenofibrate