Fluvastatin inhibits O2- and ICAM-1 levels in a rat model with aortic remodeling induced by pressure overload.
Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression is suggested to play an important role in the pathogenesis of vascular remodeling. The aim of the present study was to investigate the effects of the 3-hydroxy-3-methylglutaryl (HMG) CoA reductase inhibitor fluvastatin on superoxide anion (O2-) production and ICAM-1 expression in a rat model with vascular remodeling induced by pressure overload. Two weeks after aortic banding, marked increases in O2- production and ICAM-1 protein levels were observed in the aorta. O2- formation and ICAM-1 immunoreactivity were mainly increased in the endothelium and adventitia of the aorta in banded rats. Oral administration of fluvastatin prevented both these changes and the development of perivascular fibrosis and increased the expression of endothelial nitric oxide synthase. Cholesterol and lipid peroxide levels in serum did not change in the banded rats. Thus the beneficial effects of fluvastatin seen in this study as well as its cholesterol-lowering effect may contribute to attenuate the atherosclerotic process.
Katoh
M
M
Discovery Research Laboratory, Tanabe Seiyaku Company, Limited, Toda, Saitama 335-8505, Japan. katoh.m@tanbe.co.jp
Kurosawa
Y
Y
Tanaka
K
K
Watanabe
A
A
Doi
H
H
Narita
H
H
D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*
D004791:Enzyme Inhibitors; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D000077340:Fluvastatin; D006903:Hydroxymethylglutaryl CoA Reductases