Implitapide, a Microsomal Triglyceride Transfer Protein Inhibitor, Reduces Progression of Atherosclerosis in Apolipoprotein E Knockout Mice Fed a Western-Type Diet : Involvement of the Inhibition of Postprandial Triglyceride Elevation(Pharmacology)
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概要
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Microsomal triglyceride transfer protein (MTP) is essential for the synthesis of both chylomicron in the intestine and very low-density lipoprotein in the liver. An MTP inhibitor, (2S)-2-cyclopentyl-2-[4-[(2,4-dimethyl-9H-pyrido[2,3-b]indol-9-yl)methyl]phenyl]-N-[(1S)-2-hydroxy-l-phenylethyl]ethanamide (implitapide), has been shown to suppress atherosclerosis in apolipoprotein E knockout (apoE KO) mice. To elucidate the antiatherosclerotic mechanisms of implitapide in the mice, we examined the effects on plasma lipid levels, triglyceride (TG) elevation after oral fat loading, and development of atherosclerosis in apoE KO mice fed a Western-type diet. Implitapide at a dosage of approximately 3.2 mg/kg/day significantly reduced both total cholesterol and TG levels during the 8-week treatment period. In addition, implitapide significantly inhibited the increase in plasma TG levels after oral olive oil loading tests conducted after 4 weeks of treatment. After the treatment, implitapide significantly suppressed the atherosclerotic lesion area by 83% compared with a control group. These results provide direct evidence that the antiatherosclerotic effects of implitapide in apoE KO mice are associated with the inhibition of postprandial TG elevation, in addition to the reduction of both plasma total cholesterol and TG levels.
- 社団法人日本薬学会の論文
- 2005-02-01
著者
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MUTOH Seitaro
Medicinal Biology Research Laboratories, Astellas Pharmaceutical Inc.
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Mutoh S
Fujisawa Pharmaceutical Co. Ltd. Ibaraki Jpn
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Mutoh Seitaro
Department Of Urology Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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UESHIMA Koji
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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AKIHISA-UMENO Hitomi
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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NAGAYOSHI Akira
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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TAKAKURA Shoji
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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MATSUO Masahiko
Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Co., Ltd.
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Matsuo Mitsuyoshi
Tokyo Metropolitan Institute of Gerontology
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Nagayoshi Akira
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Nagayoshi Akira
Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Ueshima Koji
Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Takakura Shoji
Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Mutoh Seitaro
Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Akihisa-umeno Hitomi
Medicinal Biology Research Laboratories Fujisawa Pharmaceutical Co. Ltd.
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Matsuo Mitsuyoshi
Department Of Biology Faculty Of Science Konan University
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