HL-004, the ACAT inhibitor, prevents the progression of atherosclerosis in cholesterol-fed rabbits.

Abstract

HL-004, N-(2,6-diisopropylphenyl) tetradecylthioacetamide, a novel acyl-CoA:cholesterol 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.

• Authors: Y Asami, I Yamagishi, S Murakami, H Araki, K Tsuchida, S Higuchi
• Journal: Life sciences (Life Sci) Vol. 62 Issue 12 Pg. 1055-63 ( 1998) ISSN: 0024-3205 [Print] Netherlands
• PMID: 9519807 (Publication Type: Journal Article)

Chemical References

• Acetanilides
• Anticholesteremic Agents
• Cholesterol, Dietary
• Enzyme Inhibitors
• HL 004
• Lipids
• Cholesterol
• Sterol O-Acyltransferase

Topics

• Acetanilides (therapeutic use)
• Animals
• Anticholesteremic Agents (therapeutic use)
• Aorta, Thoracic (metabolism)
• Arteriosclerosis (etiology, prevention & control)
• Body Weight (drug effects)
• Cholesterol (blood)
• Cholesterol, Dietary (adverse effects)
• Disease Progression
• Eating (drug effects)
• Enzyme Inhibitors (therapeutic use)
• Lipids (blood)
• Liver (metabolism)
• Male
• Rabbits
• Sterol O-Acyltransferase (antagonists & inhibitors, metabolism)