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Is HDL quality a good candidate for novel therapeutic target of cardiovascular disease?

Research Project

Project/Area Number 15K09130
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
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)

Co-Investigator(Renkei-kenkyūsha) HARADA-SHIBA Mariko  国立循環器病研究センター, 研究所, 部長 (70271575)
MIYAMOTO Hiroshi  国立循環器病研究センター, 病院, 部長 (10312224)
WATANABE Makoto  国立循環器病研究センター, 病院, 医長 (40343446)
ASAUMI Yasuhide  国立循環器病研究センター, 病院, 医長 (20629315)
Research Collaborator MORIMOTO Megumu  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsHDL機能 / HDLコレステロール / 家族性高コレステロール血症 / 一般住民コホート / コレステロール引き抜き能 / 抗酸化能 / HDLの質 / HDL粒子組成 / 粒子組成
Outline of Final Research Achievements

Drug interventions that increase high-density lipoprotein cholesterol (HDL-C), which was thought as “the good cholesterol”, have not reduced cardiovascular events in patients already prescribed statin. These evidences support the importance of HDL functionalities over the simple measurement of HDL-C levels. We demonstrated both cholesterol efflux capacity and anti-oxidant property were better surrogate markers for predicting atherosclerotic cardiovascular disease (ASCVD) than HDL-C levels in patients with familial hypercholesterolemia. Moreover, we investigated the association between cholesterol efflux capacity and incident ASCVD outcomes in a Japanese general population cohort (The Suita study). We found cholesterol efflux capacity was inversely associated with the incidence of all ASCVD events. Further studies are needed to identify the determinants of HDL functionalities. It will lead to develop novel biomarkers and drugs to reduce residual risks after LDL lowering therapy.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (42 results)

All 2018 2017 2016 2015 Other

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results,  Acknowledgement Compliant: 1 results) Presentation (25 results) (of which Int'l Joint Research: 8 results,  Invited: 8 results) Remarks (3 results)

  • [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
      2017 Annual Research 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
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages.2017

    • Author(s)
      Furuhashi M, Ogura M, Matsumoto M, Yuda S, Muranaka A, Kawamukai M, Omori A, Tanaka M, Moniwa N, Ohnishi H, Saitoh S, Harada-Shiba M, Shimamoto K, Miura T.
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 217-217

    • DOI

      10.1038/s41598-017-00177-w

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] VLDL/LDL acts as a drug carrier and regulates the transport and metabolism of drugs in the body.2017

    • Author(s)
      Yamamoto H, Takada T, Yamanashi Y, Ogura M, Masuo Y, Harada-Shiba M, Suzuki H
    • Journal Title

      Scientific Reports

      Volume: 7 (1) Issue: 1 Pages: 633-633

    • DOI

      10.1038/s41598-017-00685-9

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] How to assess and manage cardiovascular risk associated with lipid alterations beyond LDL2017

    • Author(s)
      Averna Maurizio、Stroes Erik、Ogura Masatsune、Postadzhiyan Arman、Cercek Miha、Calabr? Paolo、Suppressa Patrizia
    • Journal Title

      Atherosclerosis Supplements

      Volume: 26 Pages: 16-24

    • DOI

      10.1016/s1567-5688(17)30021-1

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Xanthohumol, a hop-derived prenylated flavonoid, promotes macrophage reverse cholesterol transport.2017

    • Author(s)
      Hirata H, Uto-Kondo H, Ogura M, Ayaori M, Shiotani K, Ota A, Tsuchiya Y, Ikewaki K.
    • Journal Title

      J Nutr Biochem.

      Volume: 47 Pages: 29-34

    • DOI

      10.1016/j.jnutbio.2017.04.011

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] 危険因子 コレステロール引き抜き能2017

    • Author(s)
      小倉正恒
    • Journal Title

      動脈硬化予防

      Volume: 16 Pages: 100-102

    • Related Report
      2017 Annual Research Report
  • [Journal Article] FH診療-これからの展望と課題2016

    • Author(s)
      小倉正恒, 斯波真理子
    • Journal Title

      BIO Clinica

      Volume: 13 Pages: 23-27

    • Related Report
      2016 Research-status Report
  • [Journal Article] リスクファクターコントロール:脂質代謝異常-さらなるLDL-Cの低下とHDLへの介入2016

    • Author(s)
      小倉正恒, 斯波真理子
    • Journal Title

      医学のあゆみ

      Volume: 256 Pages: 689-694

    • Related Report
      2016 Research-status Report
  • [Journal Article] FH診療の展望と課題2016

    • Author(s)
      小倉正恒, 斯波真理子
    • Journal Title

      呼吸と循環

      Volume: 64 Pages: 1095-1101

    • Related Report
      2016 Research-status Report
  • [Journal Article] HDL機能と心血管疾患-FH患者からの知見-2016

    • Author(s)
      小倉正恒, 斯波真理子
    • Journal Title

      循環plus

      Volume: 17 Pages: 7-9

    • Related Report
      2016 Research-status Report
  • [Journal Article] 動脈硬化・心血管疾患を防ぐ脂質管理2016

    • Author(s)
      小倉正恒
    • Journal Title

      生活習慣病 News & Views

      Volume: 40 Pages: 3-4

    • Related Report
      2016 Research-status Report
  • [Journal Article] 家族性高コレステロール血症をめぐる最近の話題(小児を含む)2016

    • Author(s)
      小倉正恒, 斯波真理子
    • Journal Title

      Total Vascular Management

      Volume: 3 Pages: 18-22

    • Related Report
      2016 Research-status Report
  • [Journal Article] Association between Cholesterol Efflux Capacity and Atherosclerotic Cardiovascular Disease in Patients with Familial Hypercholesterolemia2016

    • Author(s)
      Masatsune Ogura, Mika Hori, Mariko Harada-Shiba.
    • Journal Title

      Arterioscler Thromb Vasc Biol.

      Volume: 36(1) Issue: 1 Pages: 181-188

    • DOI

      10.1161/atvbaha.115.306665

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [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82回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] HDLはまだ死んでいない2018

    • Author(s)
      小倉正恒
    • Organizer
      日本生物工学会 第8回学際的脂質創生研究部会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [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
      2017 Annual Research 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
    • Related Report
      2017 Annual Research Report
  • [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学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Antioxidant property of HDL and cholesterol efflux capacity as mutually independent risk markers for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia2017

    • Author(s)
      Masatsune Ogura, Megumu Morimoto, Mariko Harada-Shiba
    • Organizer
      3rd World Congress of Clinical Lipidology Congress
    • Place of Presentation
      Brisbane, Australia
    • Year and Date
      2017-02-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Antioxidant property of HDL as a novel residual risk for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia2017

    • Author(s)
      Masatsune Ogura, Megumu Morimoto, Mariko Harada-Shiba
    • Organizer
      第81回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report 2016 Research-status Report
  • [Presentation] Fatty acid-binding protein 5 as a residual risk for atherosclerotic cardiovascular disease in patients with familial hypercholesterolemia2017

    • Author(s)
      Masatsune OGURA, Masato FURUHASHI, Megumu MORIMOTO, Tetsuji MIURA, Mariko HARADA-SHIBA
    • Organizer
      85th European Atherosclerosis Society Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HDL機能測定の臨床的意義と課題2017

    • Author(s)
      小倉正恒
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 予防医学におけるHDLの量と質2017

    • Author(s)
      小倉正恒
    • Organizer
      第57回日本臨床化学会年次学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Cholesterol Efflux Capacity and Incident Atherosclerotic Cardiovascular Disease Events in a Japanese General Population2017

    • Author(s)
      Masatsune Ogura, Makoto Watanabe, Megumu Horiuchi, Yoshihiro Miyamoto, Mariko Harada-Shiba
    • Organizer
      European Society of Cardiology Congress 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] HDL機能としての抗酸化能とその臨床的意義2017

    • Author(s)
      小倉正恒
    • Organizer
      第7回学際的脂質創生研究部会(日本生物工学会)
    • Place of Presentation
      福岡
    • Related Report
      2016 Research-status Report
  • [Presentation] HDL機能評価法の確立と臨床応用2016

    • Author(s)
      小倉正恒
    • Organizer
      第56回日本臨床化学会
    • Place of Presentation
      熊本
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] Antioxidant property of high-density lipoprotein predicts the presence of atherosclerotic cardiovascular disease and corneal arcus in patients with familial hypercholesterolemia2016

    • Author(s)
      Masatsune Ogura, Megumu Morimoto, Mariko Harada-Shiba
    • Organizer
      European Society of Cardiology Congress 2016
    • Place of Presentation
      Rome, Italy
    • Year and Date
      2016-08-27
    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] FHの残余リスクとしてのHDL機能の重要性2016

    • Author(s)
      小倉正恒
    • Organizer
      第48回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-14
    • Related Report
      2015 Research-status Report
  • [Presentation] 家族性高コレステロール血症の残余リスクとしてのHDL機能2016

    • Author(s)
      小倉正恒
    • Organizer
      第48回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-13
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 家族性高コレステロール血症患者における残余リスク2016

    • Author(s)
      小倉正恒
    • Organizer
      第52回日本循環器病予防学会学術集会
    • Place of Presentation
      埼玉
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] High-Density Lipoprotein Phospholipid Content and Apolipoprotein A-I Level Are Determinants of Cholesterol Efflux Capacity in Patients with Familial Hypercholesterolemia2016

    • Author(s)
      Masatsune Ogura, Megumu Morimoto, Mariko Harada-Shiba
    • Organizer
      84th European Atherosclerosis Society Congress
    • Place of Presentation
      Innsbruck, Austria
    • Year and Date
      2016-05-29
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] High-density Lipoprotein Phospholipid Content and Apolipoprotein A-I Level Are Determinants of Cholesterol Efflux Capacity in Patients with Familial Hypercholesterolemia2016

    • Author(s)
      Masatsune Ogura, Mariko Harada-Shiba.
    • Organizer
      84th European Atherosclerosis Society Congress
    • Place of Presentation
      Innsbruck, Austria
    • Year and Date
      2016-05-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cholesterol Efflux Capacity as a Promising Marker for Atherosclerotic and Metabolic diseases2016

    • Author(s)
      Masatsune Ogura, Mariko Harada-Shiba.
    • Organizer
      第80回日本循環器学会
    • Place of Presentation
      仙台
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] HDLの量と質2016

    • Author(s)
      小倉正恒
    • Organizer
      千里循環器病セミナー
    • Place of Presentation
      大阪
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] HDL機能測定法の開発 -残余リスクの制圧を目指して-2015

    • Author(s)
      小倉正恒
    • Organizer
      第55回日本臨床化学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-10-30
    • Related Report
      2015 Research-status Report
  • [Presentation] Cholesterol Efflux Capacity in Patients with Familial Hypercholesterolemia2015

    • Author(s)
      Masatsune Ogura, Mika Hori, Mariko Harada-Shiba.
    • Organizer
      The 17th International Symposium on Atherosclerosis
    • Place of Presentation
      Amsterdam, Netherlands
    • Year and Date
      2015-05-23
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cholesterol Efflux Capacity as a Residual Risk Factor in FH Patients2015

    • Author(s)
      Masatsune Ogura
    • Organizer
      Pre-Satellite Symposium of the International Symposium on Atherosclerosis 2015
    • Place of Presentation
      Tokyo
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Cholesterol Efflux Capacity as an Emergent Biomarker in Patients with Familial Hypercholesterolemia already Prescribed Statin2015

    • Author(s)
      Masatsune Ogura, Mariko Harada-Shiba.
    • Organizer
      第79回日本循環器学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-04-24
    • Related Report
      2015 Research-status Report
  • [Remarks] HDL機能に関する研究

    • URL

      http://fh-ncvc.com/teach/

    • Related Report
      2017 Annual Research Report
  • [Remarks] HDL機能に関する研究

    • URL

      http://www.ncvc.go.jp/res/divisions/molecular_innovation_in_lipidology/10-theme03.html

    • Related Report
      2017 Annual Research Report
  • [Remarks]

    • URL

      http://fh-ncvc.com/teach/hdl%E6%A9%9F%E8%83%BD%E3%81%AB%E9%96%A2%E3%81%99%E3%82%8B%E7%A0%94%E7%A9%B6/

    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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