HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in cholesterol-fed rabbits
Y Asami, I Yamagishi, S Murakami, H Araki, K Tsuchida… - Life sciences, 1998 - Elsevier
Y Asami, I Yamagishi, S Murakami, H Araki, K Tsuchida, S Higuchi
Life sciences, 1998•ElsevierHL-004, N-(2, 6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoAxholesterol
acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of
hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25
mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total
serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses
of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2 …
acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of
hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25
mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total
serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses
of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2 …
HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoAxholesterol acyltransferase (ACAT) inhibitor, was evaluated concerning the possible prevention of hyperlipidemia and atherosclerosis in 1% cholesterol-fed rabbits. HL-004 (0.2, 5 and 25 mg/kg) was orally administered once a day for 12 weeks. HL-004 inhibited the rise of total serum cholesterol at a dose of 5 mg/kg and over. In the thoracic aorta, HL-004 at the doses of 5 mg/kg and 25 mg/kg reduced the total cholesterol content by 56.3% and 84.2% compared with control, and decreased ACAT activity, dose-dependently. HL-004 also attenuated the development of aortic lesions. The area of atherosclerotic lesions was reduced by 30.3% with 5 mg/kg of HL-004 and 100% with 25 mg/kg. In this study, we suggest that the main reason for HL-004 preventing the progression of atherosclerosis is its hypocholesterolemic effect due to the inhibition of cholesterol absorption in the intestine.
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