| Project/Area Number |
25461379
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | National Defense Medical College |
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Principal Investigator |
Ikewaki Katsunori 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, その他部局等, 教授 (40287199)
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| Co-Investigator(Kenkyū-buntansha) |
AYAORI Makoto 防衛医科大学校, 医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究・病院, 助教 (70532464)
川尻 剛照 金沢大学, 医学系, 准教授 (90345637)
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| Co-Investigator(Renkei-kenkyūsha) |
KAWASHIRI Masaaki 金沢大学, 大学病院, 講師 (90345637)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 家族性高コレステロール血症 / PCSK9 / アポ蛋白B / 安定同位体 / トレーサー / FH / IDOL / stable isotope / tracer |
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| Outline of Final Research Achievements |
We performed tracer studies using stable isotope technology in order to assess in vivo kinetics of apoB in 2 homozygous FH patients with PCSK9 gene mutation (E32K). In vivo kinetic study revealed that VLDL, IDL, and LDL apoB FCR were markedly delayed as compared with controls. With regard to production rates, VLDL and IDL PR were increased, but LDL apoB PR remained unchanged. Finally, analysis of metabolic channeling demonstrated that VLDL tended to be metabolized to remnant before converting to IDL. In one patient, atorovastatin was administrated and tracer study was repeated under medication. Atorvastatin significantly improved VLDL catabolism and completely normalized IDL and LDL FCR, but imcreased VLDL remnant formation remained unchanged. In summary, tracer study revealed that FH with PCSK9 gene mutation have apoB metabolic abnormalities distinct from those with LDL receptor gene mutations.
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