Development of a new trategy for low HDL in homogygous FH patients
Project/Area Number |
20K08439
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 53020:Cardiology-related
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Research Institution | National Defense Medical College |
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、共同利用研究施設、病院並びに防衛, 内科学, 教授 (40287199)
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Co-Investigator(Kenkyū-buntansha) |
小倉 正恒 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30532486)
末永 由美子 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、共同利用研究施設、病院並びに防衛, 内科学, 助教 (30815337)
佐々木 誠 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、共同利用研究施設、病院並びに防衛, 内科学, 助教 (60837251)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | FH / HDL / apoA-I / apoA-II / stable isotope / catabolism / 家族性高コレステロール血症 / アポ蛋白A-I / アポ蛋白A-II / 安定同位体 / 異化速度 / 産生速度 / 安定同意体 / トレーサー / HDL機能 |
Outline of Research at the Start |
安定同位体は、ヒトの体内での蛋白代謝動体を評価できる方法で、海外では放射活性物質で蛋白をラベルする方法が実施可能であるが、我が国ではできないため、この安定同位体方が唯一の実験手段である。家族性高コレステロール血症(FH)はLDL高値が注目されているが、こう動脈硬化性リポ蛋白であるHDLが低く、これがFHの心血管リスクをさらに高めることがわかっており、低HDL血症の病態解明が必要である。加えて、HDLは濃度(量)ではなく機能(質)が重要との認識が高まっており、FHにおいてHDLの質の異常の検討も重要である。本研究では、FHでの低HDL血症の病態をHDL機能を評価する。
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Outline of Final Research Achievements |
FH homozygote is considered to be very high risk for atherosclerosis. Low HDL-C contribute in part for the increased atherosclerosis risk. Therefore, we aimed to elucidate kinetic pathophysiology for low HDL. We performed in vivo kinetic studies using endogenously-labeled stable isotope in 7 FH homozygotes. Kinetic studies revealed that fractional catabolic rates of apoA-I and apoA-II, major constituents of HDL, were markedly increased by about 50% as compared with control subjects with relatively unchanged synthetic rates. Therefore, low HDL levels was primarily due to increased catabolism in FH homozygotes. These findings may imply that therapy such as CETP inhibitors can normalized increased catabolic rates, thereby normalizing HDL-C in FH homozygotes. This may be a novel therapeutic strategy for treatment-resistant homozygous FH patients.
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Academic Significance and Societal Importance of the Research Achievements |
FH homozygotes needs early and effective treatment. The present study discovered that increased catabolic rate caused low HDL-C, another additive atheroscleritic risk. Based on our findings, we may develop a new therapy to nomalize catbolism to reduce the risk in FH homozygotes.
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Report
(4 results)
Research Products
(36 results)
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[Journal Article] Effects of Dietary Education Program for the Japan Diet on Cholesterol Efflux Capacity: A Randomized Controlled Trial2022
Author(s)
Umezawa A, Maruyama C, Endo T, Suenaga Y, Shijo Y, Kameyama N, Sato A, Nishitani A, Ayaori M, Waki M, Teramoto T, Ikewaki K
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 29
Issue: 6
Pages: 881-893
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2022-06-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation2022
Author(s)
Komatsu T , Ayaori M, Uto-Kondo H, Hayashi K, Tamura K, Sato H, Sasaki M, Nishida T, Takiguchi S, Yakushiji E, Nakaya K, Ikewaki K
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 29
Issue: 5
Pages: 775-784
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2022-05-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Effects of Nutrition Education Program for the Japan Diet on Serum LDL-Cholesterol Concentration in Patients with Dyslipidemia: A Randomized Controlled Trial2021
Author(s)
Chizuko Maruyama, Yuri Shijo, Noriko Kameyama, Ariko Umezawa, Aisa Sato, Ai Nishitani, Makoto Ayaori, Katsunori Ikewaki, Masako Waki, Tamio Teramoto
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 28
Issue: 10
Pages: 1035-1051
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2021-10-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Diagnosis and Management of Sitosterolemia 20212021
Author(s)
Tada H, Nomura A, Ogura M, Ikewaki K, Ishigaki Y, Inagaki K, Tsukamoto K, Dobashi K, Nakamura K, Hori M, Matsuki K, Yamashita S, Yokoyama S, Kawashiri MA, Harada-Shiba M.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 28
Issue: 8
Pages: 791-801
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2021-08-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] Current Status of Familial LCAT Deficiency in Japan2021
Author(s)
Kuroda Masayuki、Bujo Hideaki、Yokote Koutaro、Murano Takeyoshi、Yamaguchi Takashi、Ogura Masatsune、Ikewaki Katsunori、Koseki Masahiro、Takeuchi Yasuo、Nakatsuka Atsuko、Hori Mika、Matsuki Kota、Miida Takashi、Yokoyama Shinji、Wada Jun、Harada-Shiba Mariko.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 28
Issue: 7
Pages: 679-691
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2021-07-01
Related Report
Peer Reviewed / Open Access
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[Journal Article] High-Density Lipoprotein Cholesterol Efflux Capacity as a Novel Prognostic Surrogate for Coronary Artery Disease2021
Author(s)
Hisauchi I, Ishikawa T, Ayaori M, Uto-Kondo H, Koshikawa Y, Ukaji T, Nakamura H, Mizutani Y, Taguchi I, Nakajima T, Mutoh M, Ikewaki K.
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Journal Title
Journal of Atherosclerosis and Thrombosis
Volume: 28
Issue: 7
Pages: 696-702
DOI
NAID
ISSN
1340-3478, 1880-3873
Year and Date
2021-07-01
Related Report
Peer Reviewed / Open Access
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[Presentation] Cholesterol efflux capacity (CEC) as a negative predictor of coronary artery disease -From the analysis with newly discovered glycometabolic parameters-2021
Author(s)
Sasaki M, Ezaki H, Ayaori M, Takahiro M, Ochi S, Arakawa J, Suenaga Y, Endo Y, Teramoto M, Sakurada M, Matsuura T, Ikewaki K
Organizer
ISA2021
Related Report
Int'l Joint Research
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[Presentation] Lack of association of high-density lipoprotein cholesterol efflux capacity (CEC) with glycometabolic parameters in patients with ischemic heart disease2021
Author(s)
Makoto Sasaki, Hirotaka Ezaki, Makoto Ayaori, Masaki Takahiro, Sae Ochi, Junko Arakawa, Yumiko Suenaga, Yasuhiro Endo, Manami Teramoto, Masami Sakurada, Tomokazu Matsuura, Katsunori Ikewaki
Organizer
第85回日本循環器学会学術集会
Related Report
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