Effect of fluvastatin sodium on the smooth muscle cells in atherosclerotic plaques. In vivo study using low-density lipoprotein receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbits.
The effects of fluvastatin sodium (CAS 93957-55-2, XU 62-320), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the smooth muscle cells in the atherosclerotic plaques of Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, were examined. Fluvastatin was administered to WHHL rabbits for 32 weeks at a dose of 50 mg/kg of body weight. The control WHHL rabbits were administered distilled water as placebo. Compared to the control group, the total cholesterol levels in the sera, very low density lipoprotein, intermediate density lipoprotein, and LDL decreased by 34%, 72%, 63%, and 25%, respectively. Although the surface lesion area of the aorta in the treated group was not different from that in the control group, intimal thickening in the treated group was significantly lower than that in the control group. Of the lesional components of atherosclerosis, the relative area of smooth muscle cells, collagen fibers, and extracellular lipid deposits in the treated group decreased significantly. It is concluded that fluvastatin decreased in the smooth muscle cell content of the atherosclerotic plaques and delayed progression of the aortic atherosclerosis in addition to the potent hyperlipidemic effect.
Institute for Experimental Animals, Kobe University School of Medicine, Japan.
M
M
Shiomi
T
T
Ito
T
T
Tsukada
M
M
Shiraishi
T
T
Yata
D000818:Animals; D000911:Antibodies, Monoclonal; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D002784:Cholesterol / Q000097:blood; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology*; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics
D000911:Antibodies, Monoclonal; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D008055:Lipids; D008074:Lipoproteins; D011973:Receptors, LDL; D000077340:Fluvastatin; D002784:Cholesterol