Anti-atherosclerotic effect of E5324, an inhibitor of acyl-CoA:cholesterol acyltransferase, in Watanabe heritable hyperlipidemic rabbits
| Autor: | Teiji Kimura, Hiroko Kobayashi, Shinji Yoshitake, Takao Saeki, Issei Ohtsuka, Toshie Yamada, Hiroshi Tanaka, Motoji Kogushi, Isao Saito, Hironobu Hiyoshi, Masahiro Takada, Mamoru Yanagimachi |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Aortic arch medicine.medical_specialty Arteriosclerosis Sterol O-acyltransferase Probucol Aorta Thoracic Hyperlipidemias Biology chemistry.chemical_compound medicine.artery Internal medicine Hyperlipidemia medicine Animals Thoracic aorta Enzyme Inhibitors Analysis of Variance Aorta Cholesterol Phenylurea Compounds Organ Size Lipid Metabolism medicine.disease Diet Disease Models Animal Endocrinology chemistry Chromatography Thin Layer Rabbits Cardiology and Cardiovascular Medicine Sterol O-Acyltransferase medicine.drug |
| Zdroj: | Atherosclerosis. 124:203-210 |
| ISSN: | 0021-9150 |
| DOI: | 10.1016/0021-9150(96)05831-5 |
| Popis: | E5324, n-butyl-N'-[2-[3-(5-ethyl-4-phenyl-1H-imidazol-1-yl)propoxy]-6- methylphenyl]urea, a novel and potent inhibitor of acyl-CoA:cholesterol acyltransferase (ACAT), was evaluated for its anti-atherosclerotic and lipid-lowering effects in Watanabe heritable hyperlipidemic (WHHL) rabbits. At 3 months of age, 40 male WHHL rabbits were divided into 4 groups. The rabbits were fed a standard rabbit chow (control group), or standard rabbit chow containing E5324 (0.1% or 0.02%) or 1% probucol for 16 weeks. Even the high dose of E5324 did not lower the plasma total cholesterol levels throughout the experiment. Probucol slightly reduced the plasma cholesterol levels, and showed anti-atherosclerotic activity, i.e., reductions of atherosclerotic plaque formation and cholesterol content in the aorta. Although E5324 did not lower plasma cholesterol, atherosclerotic plaque formation in the aortic arch and thoracic aorta was reduced (by about 34% and 41%, respectively, at the high dose; P < 0.05). Cholesterol content in the aortic arch and thoracic aorta was also reduced (by about 59% and 62% at the high dose, respectively) compared with the control. These results suggest that E5324 acts directly on the arterial wall through ACAT inhibition, and prevents the progression of atherosclerosis in WHHL rabbits. |
| Databáze: | OpenAIRE |
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