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Residual risk control in familial hypercholesterolemia: Identification of lipids responsible for HDL malignant transformation

Research Project

Project/Area Number 18K08125
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Ogura Masatsune  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)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsHDL機能 / 家族性高コレステロール血症 / 動脈硬化予防 / コレステロール搬出能 / リン脂質 / ホスフォリパーゼ / ASCVD / 脂肪酸側鎖 / 冠動脈疾患 / 高密度リポ蛋白 / 残余リスク
Outline of Final Research Achievements

In this research project, we searched for the lipids that are responsible for making HDL bad in patients with familial hypercholesterolemia (FH). We have previously reported that cholesterol efflux capacity is a more useful residual risk marker than HDL-C levels in patients with FH. However, we faced the challenge of not being able to standardize the method for measuring the efflux capacity. We decided to overcome the problem by identifying the true bad lipids, which are common to both impaired efflux capacity and coronary artery disease, among the HDL components. Therefore, we performed lipidomic analysis of patient HDL fractions and identified several lipid species that were negatively associated with efflux capacity and positively associated with atherosclerosis severity.

Academic Significance and Societal Importance of the Research Achievements

本研究の達成は引き抜き能に代わる動脈硬化予測バイオマーカーの確立や創薬(得られた脂質分子の阻害薬)の基盤を築く。家族性高コレステロール血症(FH)患者のHDL代謝は非FHと大きな差異はないため、全ハイリスク患者におけるLDL-C低下治療後の残余リスク制圧につながる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (43 results)

All 2022 2021 2020 2019 2018

All Journal Article (17 results) (of which Peer Reviewed: 14 results,  Open Access: 10 results) Presentation (22 results) (of which Int'l Joint Research: 4 results,  Invited: 12 results) Book (4 results)

  • [Journal Article] A Resuscitated Case of Acute Myocardial Infarction with both Familial Hypercholesterolemia Phenotype Caused by Possibly Oligogenic Variants of the <i>PCSK9</i> and <i>ABCG5</i> Genes and Type I CD36 Deficiency2022

    • Author(s)
      Nishikawa Ryo、Furuhashi Masato、Hori Mika、Ogura Masatsune、Harada-Shiba Mariko、Okada Takeshi、Koseki Masahiro、Kujiraoka Takeshi、Hattori Hiroaki、Ito Ryosuke、Muranaka Atsuko、Kokubu Nobuaki、Miura Tetsuji
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 29 Issue: 4 Pages: 551-557

    • DOI

      10.5551/jat.58909

    • NAID

      130007992205

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2022-04-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Reason is Still Unclear2022

    • Author(s)
      Ogura Masatsune
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 29 Issue: 1 Pages: 3-4

    • DOI

      10.5551/jat.ED164

    • NAID

      130008138916

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2022-01-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Patients With LDLR and PCSK9 Gene Variants Experienced Higher Incidence of Cardiovascular Outcomes in Heterozygous Familial Hypercholesterolemia2021

    • Author(s)
      Doi Takahito、Hori Mika、Harada‐Shiba Mariko、Kataoka Yu、Onozuka Daisuke、Nishimura Kunihiro、Nishikawa Ryo、Tsuda Kosuke、Ogura Masatsune、Son Cheol、Miyamoto Yoshihiro、Noguchi Teruo、Shimokawa Hiroaki、Yasuda Satoshi
    • Journal Title

      Journal of the American Heart Association

      Volume: 10 Issue: 4

    • DOI

      10.1161/jaha.120.018263

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Achilles Tendon Softness as a New Tool for Diagnosing Familial Hypercholesterolemia2021

    • Author(s)
      Michikura Masahito、Ogura Masatsune、Hori Mika、Furuta Kenji、Hosoda Kiminori、Harada-Shiba Mariko
    • Journal Title

      JACC: Cardiovascular Imaging

      Volume: - Issue: 7 Pages: 1483-1485

    • DOI

      10.1016/j.jcmg.2021.01.033

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Guidelines on the Clinical Evaluation of Medicinal Products for Treatment of Dyslipidemia2020

    • Author(s)
      Yamashita Shizuya、Kouji Kajinami, et al.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 27 Issue: 11 Pages: 1246-1254

    • DOI

      10.5551/jat.CR004

    • NAID

      130007933950

    • ISSN
      1340-3478, 1880-3873
    • URL

      https://pure.teikyo.jp/en/publications/02e4e9dc-386d-44e8-93dd-22ca589512fb

    • Year and Date
      2020-11-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The benign c.344G>A: p.(Arg115His) variant in the LDLR gene interpreted from a pedigree-based genetic analysis of familial hypercholesterolemia.2020

    • Author(s)
      Hori M*(corresponding author), Takahashi A, Son C, Ogura M, Harada-Shiba M*
    • Journal Title

      Lipids in Health and Disease

      Volume: - Issue: 1 Pages: 62-62

    • DOI

      10.1186/s12944-020-01252-4

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The first Japanese cases of familial hypercholesterolemia due to a known pathogenic APOB gene variant, c.10580?G>A: p.(Arg3527Gln)2020

    • Author(s)
      Hori Mika、Takahashi Atsushi、Son Cheol、Ogura Masatsune、Harada-Shiba Mariko
    • Journal Title

      Journal of Clinical Lipidology

      Volume: 14 Issue: 4 Pages: 482-486

    • DOI

      10.1016/j.jacl.2020.05.007

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 脂質がつなぐもの:生物工学的脂質研究が導く新しい学際研究と産業(後編)】HDLはまだ死んでいない2020

    • Author(s)
      小倉正恒
    • Journal Title

      生物工学会誌

      Volume: 98 Pages: 536-539

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 家族性高コレステロール血症ホモ接合体の管理2020

    • Author(s)
      小倉正恒
    • Journal Title

      糖尿病・内分泌代謝科

      Volume: 51 Pages: 157-163

    • NAID

      40022335306

    • Related Report
      2020 Annual Research Report
  • [Journal Article] 【もっともっとくわしく知りたい!イラストでわかる脂質・脂肪酸・コレステロールのふしぎ】続発性脂質異常症2020

    • Author(s)
      小倉正恒
    • Journal Title

      Nutrition Care

      Volume: 13 Pages: 335-338

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Familial Hypercholesterolemia and Lipoprotein Apheresis2019

    • Author(s)
      Makino Hisashi、Koezuka Ryo、Tamanaha Tamiko、Ogura Masatsune、Matsuki Kota、Hosoda Kiminori、Harada-Shiba Mariko
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 26 Issue: 8 Pages: 679-687

    • DOI

      10.5551/jat.RV17033

    • NAID

      130007686515

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2019-08-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of LDLR and PCSK9 pathogenic variants in Japanese heterozygous familial hypercholesterolemia patients2019

    • Author(s)
      Hori Mika、Ohta Naotaka、Takahashi Atsushi、Masuda Hiroaki、Isoda Rieko、Yamamoto Suguru、Son Cheol、Ogura Masatsune、Hosoda Kiminori、Miyamoto Yoshihiro、Harada-Shiba Mariko
    • Journal Title

      Atherosclerosis

      Volume: 289 Pages: 101-108

    • DOI

      10.1016/j.atherosclerosis.2019.08.004

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Statement for Appropriate Clinical Use of PCSK9 Inhibitors2018

    • Author(s)
      Nohara Atsushi、Ohmura Hirotoshi、Okazaki Hiroaki、Ogura Masatsune、Kitagawa Kazuo、Koseki Masahiro、Sato Kayoko、Tsukamoto Kazuhisa、Yamashita Shizuya、On behalf of the Japan Atherosclerosis Society Working Group on Statement for Appropriate Use of PCSK9 Inhibitors
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 8 Pages: 747-750

    • DOI

      10.5551/jat.45229

    • NAID

      130007429079

    • ISSN
      1340-3478, 1880-3873
    • URL

      https://pure.teikyo.jp/en/publications/c296d3d6-deb0-4fd5-b37a-993a05d438f2

    • Year and Date
      2018-08-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guidelines for Diagnosis and Treatment of Familial Hypercholesterolemia 20172018

    • Author(s)
      Harada-Shiba Mariko、Arai Hidenori、Ishigaki Yasushi、Ishibashi Shun、Okamura Tomonori、Ogura Masatsune、Dobashi Kazushige、Nohara Atsushi、Bujo Hideaki、Miyauchi Katsumi、Yamashita Shizuya、Yokote Koutaro、Working Group by Japan Atherosclerosis Society for Making Guidance of Familial Hypercholesterolemia
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 8 Pages: 751-770

    • DOI

      10.5551/jat.CR003

    • NAID

      130007429791

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2018-08-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Guidance for Pediatric Familial Hypercholesterolemia 20172018

    • Author(s)
      Harada-Shiba Mariko、Ohta Takao、Ohtake Akira、Ogura Masatsune、Dobashi Kazushige、Nohara Atsushi、Yamashita Shizuya、Yokote Koutaro、Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 6 Pages: 539-553

    • DOI

      10.5551/jat.CR002

    • NAID

      130007382567

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2018-06-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hepatic Overexpression of Endothelial Lipase Lowers HDL (High-Density Lipoprotein) but Maintains Reverse Cholesterol Transport in Mice2018

    • Author(s)
      Takiguchi Shunichi、Ayaori Makoto、Yakushiji Emi、Nishida Takafumi、Nakaya Kazuhiro、Sasaki Makoto、Iizuka Maki、Uto-Kondo Harumi、Terao Yoshio、Yogo Makiko、Komatsu Tomohiro、Ogura Masatsune、Ikewaki Katsunori
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 印刷中 Issue: 7 Pages: 1454-1467

    • DOI

      10.1161/atvbaha.118.311056

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] PCSK9 inhibition in the management of familial hypercholesterolemia2018

    • Author(s)
      Ogura Masatsune
    • Journal Title

      Journal of Cardiology

      Volume: 71 Issue: 1 Pages: 1-7

    • DOI

      10.1016/j.jjcc.2017.07.002

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] PCSK9阻害薬がLDL-C低下に有効であった小児FHホモ接合体の一例2020

    • Author(s)
      松木 恒太 , 小倉 正恒 , 山本 雅 , 堀 美香 , 斯波 真理子
    • Organizer
      第33回小児脂質研究会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 循環器疾患患者の妊娠と出産2020

    • Author(s)
      小倉 正恒 , 神谷 千津子 , 片岡 有 , 吉松 淳 , 斯波 真理子
    • Organizer
      第84回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 家族性高コレステロール血症患者におけるアキレス腱厚の未治療時およびスタチン服用による変化2020

    • Author(s)
      道倉 雅仁 , 小倉 正恒 , 斯波 真理子
    • Organizer
      第52回日本動脈硬化学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人家族性高コレステロール血症スクリーニングに用いる「超音波によるアキレス腱厚測定」の標準的評価法 超音波を用いたアキレス腱厚計測2020

    • Author(s)
      道倉 雅仁 , 小倉 正恒 , 斯波 真理子
    • Organizer
      第52回日本動脈硬化学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 原発性脂質異常症の分子メカニズムと治療との関連 タンジール病の治療は可能か?2020

    • Author(s)
      小倉 正恒
    • Organizer
      第52回日本動脈硬化学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] FHの診断治療の進歩と課題(小児を含む) FH診断基準の方向性2020

    • Author(s)
      小倉 正恒
    • Organizer
      第52回日本動脈硬化学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 原発性脂質異常症のスクリーニング HDL異常低値・異常高値の話題と原発性脂質異常症の診療・研究の方向性について2020

    • Author(s)
      小倉 正恒
    • Organizer
      第60回日本臨床化学会学術集会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Lipidomic analysis for the prediction of cholesterol efflux capacity and atherosclerotic cardiovascular disease among patients with familial hypercholesterolemia2019

    • Author(s)
      Ogura M, Takeda H, Izumi Y, Hori M, Matsuki K, Ymamamoto M, Bamba T, Harada-Shiba M
    • Organizer
      International Conference on the Bioscience of Lipids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Identification of bad lipids in HDL fraction which predict both decreased cholesterol efflux capacity and the severity of atherosclerosis2019

    • Author(s)
      Ogura M, Takeda H, Izumi Y, Hori M, Matsuki K, Ymamamoto M, Bamba T, Harada-Shiba M
    • Organizer
      International Atherosclerosis Society 2019 HDL Workshop
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] HDLの善悪を考える2019

    • Author(s)
      小倉正恒
    • Organizer
      第33回日本小児脂質研究会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] FHを忘れない2019

    • Author(s)
      小倉正恒
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 小児と妊娠可能女性に関する諸問題2019

    • Author(s)
      小倉正恒
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] FH診断におけるアキレス腱評価2019

    • Author(s)
      小倉正恒
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] 家族性高コレステロール血症患者におけるHDL分画中リン脂質クラスとコレステロール引き抜き能および動脈硬化との関連2019

    • Author(s)
      小倉正恒
    • Organizer
      第51回日本動脈硬化学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 高LDLコレステロール血症に潜む身近な遺伝病~家族性高コレステロール血症(FH)のスクリーニングを学ぶ~2019

    • Author(s)
      小倉正恒
    • Organizer
      第11回日本肥満学会スキルアップセミナー
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Association between alpha-tocopherol concentration in HDL fraction and cholesterol efflux capacity in patients with familial hypercholesterolemia2018

    • Author(s)
      Masatsune Ogura, Yuji Hirowatari, Daisuke Manita, Mariko Harada-Shiba
    • Organizer
      European Atherosclerosis Society Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical significance of apolipoprotein E-containing HDL cholesterol/total HDL cholesterol ratio in patients with familial hypercholesterolemia2018

    • Author(s)
      Masatsune Ogura, Yasuki Ito, Mariko Harada-Shiba
    • Organizer
      59th International Conference on the Bioscience of Lipids
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] HDLの量と質2018

    • Author(s)
      小倉 正恒
    • Organizer
      第61回日本糖尿病学会年次学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 家族性高コレステロール血症ホモ接合体(HoFH)におけるコレステロール引き抜き能2018

    • Author(s)
      小倉 正恒, 堀 美香, 斯波 真理子
    • Organizer
      第50回日本動脈硬化学会 総会・学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] FH診断基準を再考する2018

    • Author(s)
      小倉 正恒
    • Organizer
      第50回日本動脈硬化学会 総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] Cholesterol efflux capacity and incident atherosclerotic cardiovascular disease events in a Japanese general population: The Suita Study2018

    • Author(s)
      Masatsune Ogura, Makoto Watanabe, Megumu Horiuchi, Yoshihiro Miyamoto, Mariko Harada-Shiba
    • Organizer
      第50回日本動脈硬化学会 総会・学術集会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] 家族性高コレステロール血症患者におけるHDL分画中のαトコフェロール濃度とコレステロール引き抜き能、動脈硬化との関連2018

    • Author(s)
      小倉 正恒, 廣渡 祐史, 真仁田 大輔 斯波 真理子
    • Organizer
      第55回日本臨床分子医学会 学術集会
    • Related Report
      2018 Research-status Report
  • [Book] そうだったんだ! 脂質異常症 : 治療の新潮流を探る2020

    • Author(s)
      伊藤浩
    • Total Pages
      262
    • Publisher
      文光堂
    • Related Report
      2020 Annual Research Report
  • [Book] あなたも名医!評価・処方の“いま”を押さえる 見直し!脂質異常症2020

    • Author(s)
      小倉正恒
    • Total Pages
      208
    • Publisher
      日本医事新報社
    • ISBN
      9784784966707
    • Related Report
      2020 Annual Research Report
  • [Book] 高齢者の循環器診療Q&A : 快適な人生を過ごしてもらう診療のツボ2020

    • Author(s)
      伊藤浩
    • Total Pages
      191
    • Publisher
      文光堂
    • Related Report
      2020 Annual Research Report
  • [Book] そうだったんだ!脂質異常症 第2版2020

    • Author(s)
      小倉正恒
    • Total Pages
      14
    • Publisher
      文光堂
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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