| Project/Area Number |
12670712
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Fukuoka University |
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Principal Investigator |
SAKU Keijiro Fukuoka Univ, School of Medicine, Professor, 医学部, 教授 (40183371)
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| Co-Investigator(Kenkyū-buntansha) |
OHTA Takao Ryukyu Univ, School of Medicine, Professor, 医学部, 教授 (70185271)
JIMI Shiro Fukuoka Univ, School of Medicine, Assist. Prof., 医学部, 助手 (30226360)
IDEISHI Munehito Fukuoka Univ, School of Medicine, Professor, 医学部, 教授 (20131807)
TASHIRO Eiichiro Fukuoka Dental College, Associate Professor, 助教授 (20271439)
NODA Keita Fukuoka Univ, School of Medicine, Lecturer, 医学部, 講師 (70289536)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | High density lipoprotein / apo HDL kinetics / CETP / Apolipoprotein A-l / CETP inhibitor / apo A-l mRNA / 生対内アポHDL代謝回転 / アポリポ蛋白A-1 / アポA-1 mRNA / アポリポ蛋白 A-I / SRB1 / ヒトCETP-Tgマウス |
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| Research Abstract |
Background: CETP plays an important role in the reverse cholesterol transport. Inhibition of CETP activity by a CETP inhibitor, JTT-705, increases serum apo A-l levels and inhibits atherosclerosis. To clarify the mechanism by which CETP inhibition increases HDL levels, we examined the effects of JTT-705 on the in vivo kinetics properties of apo A-l in cholesterol-fed rabbits. Methods: Japanese White rabbits were randomly selected to be fed with (a) a normal rabbit chow, LRC-4 (n=10), (b) a diet containing 0.2% cholesterol (n=9), or (c) admixture of (b) and 0.75% JTT-705 (n=7) for 7 mo. CETP activities and serum levels of lipoproteins were measured. In vivo apo A-l kinetics was performed by injecting radioiodinated apo A-l at the end of the study. Results: JTT-705 inhibited 38.5% of the CETP activity in cholesterol-fed rabbits. Cholesterol-feeding decreased SR [8.3 ± 1.1 vs. 10.1 ± 1.8 mg/Kg/day] and serum levels of apo A-l and increased FCR [0.61 ± 0.07 vs. 0.52 ± 0.09 /day] compared with normal chow-feeding. JTT-705 normalized the reduced SR [11.2 ± 2.9 mg/Kg/day] and serum levels of apo A-l and the increased FCR [0.50 ± 0.06 /day] in cholesterol-fed rabbits. Conclusion: Inhibition of CETP activity favorably affects the lipoprotein metabolism in cholesterol-fed rabbits, suggesting that CETP inhibition may be a therapeutic approach for atherosclerosis.
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