Lipoprotein kinetics in patients with familial hypercholesterolemia due to PCSK9 mutation
| 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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Report
(4 results)
Research Products
(33 results)
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[Journal Article] Probucol Oxidized Products, Spiroquinone and Diphenoquinone, Promote Reverse Cholesterol Transport in Mice2016
Author(s)
Yakushiji E, Ayaori M, Nishida T, Shiotani K, Takiguchi S, Nakaya K, Uto-Kondo H, Ogura M, Sasaki M, Yogo M, Komatsu T, Lu R, Yokoyama S, Ikewaki K
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 36
Pages: 591-597
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Intensive lipid lowering therapy with titrated rosuvastatin yields greater atherosclerotic aortic plaque regression: Serial magnetic resonance imaging observations from RAPID study.2014
Author(s)
76.Yogo, M., Sasaki, M., Ayaori, M., Kihara, T., Sato, H., Takiguchi, S., Uto-Kondo, H., Yakushiji, E., Nakaya, K., Komatsu, T., Momiyama, Y., Nagata, M., Mochio, S., Iguchi, Y. and Ikewaki, K.
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Journal Title
Atherosclerosis
Volume: 232
Pages: 31-39
Related Report
Peer Reviewed
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[Journal Article] Hepatic overexpression of idol increases circulating protein convertase subtilisin/kexin type 9 in mice and hamsters via dual mechanisms: sterol regulatory element-binding protein 2 and low-density lipoprotein receptor-dependent pathways.2014
Author(s)
Sasaki M, Terao Y, Ayaori M, Uto-Kondo H, Iizuka M, Yogo M, Hagisawa K, Takiguchi S, Yakushiji E, Nakaya K, Ogura M, Komatsu T, Ikewaki K.
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Journal Title
Arterioscler Thromb Vasc Biol.
Volume: 34
Pages: 1171-8
Related Report
Peer Reviewed
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[Journal Article] Ezetimibe enhances macrophage reverse cholesterol transport in hamsters: contribution of hepato-biliary pathway.2014
Author(s)
Uto-Kondo H, Ayaori M, Sotherden GM, Nakaya K, Sasaki M, Yogo M, Komatsu T, Takiguchi S, Yakushiji E, Ogura M, Nishida T, Endo Y, Ikewaki K.
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Journal Title
Biochim Biophys Acta.
Volume: 184
Pages: 1247-55
Related Report
Peer Reviewed
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[Journal Article] Citrulline increases cholesterol efflux from macrophages in vitro and ex vivo via ATP-binding cassette transporters.2014
Author(s)
Uto-Kondo H, Ayaori M, Nakaya K, Takiguchi S, Yakushiji E, Ogura M, Terao Y, Ozasa H, Sasaki M, Komatsu T, Sotherden GM, Hosoai T, Sakurada M, Ikewaki K.
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Journal Title
J Clin Biochem Nutr.
Volume: 55
Pages: 32-9
NAID
Related Report
Peer Reviewed
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