Inhibitory effect of TS-962 on the formation of early atherosclerotic lesions in high fat-fed hyperlipidemic hamsters.
The hypocholesterolemic and anti-atherosclerotic effect of TS-962, a specific ACAT inhibitor, was investigated in a hamster model fed a high fat diet containing 10% coconut oil and 0.05% cholesterol. Lipid accumulated atherosclerotic lesions were detected by using oil red O staining in the lesion-prone aortic arch. A high dose, estimated to be 15 mg/kg, of TS-962 decreased serum cholesterol to normal levels with reduction of liver cholesterol contents below normal levels, and as a consequence, entirely inhibited the lipid accumulation in the aortic arch. Furthermore, a low dose, estimated to be 1.5 mg/kg, of TS-962 remarkably inhibited aortic lipid accumulation by 73% compared with the control group, without changing either serum cholesterol level or liver cholesterol content. These findings suggest that TS-962 is effective in the primary prevention of atherosclerosis by directly suppressing the formation of foam cells in arteries.
Asami
Y
Y
Pharmaceutical Research Laboratories, Taisho Pharmaceutical Co. Ltd., Ohmiya, Saitama, Japan. s10960@ccm.taisho.co.jp
Yamagishi
I
I
Akiyoshi
K
K
Tomoike
H
H
Tsuchida
K
K
Higuchi
S
S
D000081:Acetamides / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001835:Body Weight; D006224:Cricetinae; D004041:Dietary Fats / Q000633:toxicity*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006949:Hyperlipidemias / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000081:Acetamides; D004041:Dietary Fats; D004791:Enzyme Inhibitors; C401889:TS 962; D002785:Sterol O-Acyltransferase