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 specif ic ACAT inhibitor, was investigated in a hamster model fed a high fat diet containing 10% coconut oil and 0.05% cholesterol. Lipid accumulated atheros clerotic lesions were detected by using oil red O staining in the lesion-pr one 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 con tents below normal levels. and as a consequence, entirely inhibited the lip id accumulation in the aortic arch. Furthermore. a low dose. estimated to b e 1.5 mg/kg, of TS-962 remarkably inhibited aortic lipid accumulation by 73 % compared with the control group. without changing either serum cholestero l level or liver cholesterol content. These findings suggest that TS-962 is effective in the primary prevention of atherosclerosis by directly suppres sing the formation of foam cells in arteries. (C) 1999 Elsevier Science Ire land Ltd. All rights reserved.