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Clinical utility of cholesterol uptake capacity, a novel indicator for HDL functionality

Research Project

Project/Area Number 18K08073
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKobe University

Principal Investigator

Toh Ryuji  神戸大学, 医学研究科, 特命准教授 (50379418)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords高比重リポ蛋白(HDL) / コレステロール取り込み能 / 動脈硬化 / 高比重リポ蛋白(HDL) / 心血管病 / 高比重リポ蛋白 / コレステロール逆転送
Outline of Final Research Achievements

Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as “cholesterol uptake capacity (CUC)”. We investigated the cross-sectional relationship between CUC and the morphological features of angiographic stenosis by OCT, and revealed that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation. We also demonstrated that impaired CUC is the risk for incidence of target-lesion revascularization.

Academic Significance and Societal Importance of the Research Achievements

HDLはコレステロール引抜きに加え多彩な抗動脈硬化作用を有するも、慢性炎症や糖尿病などの病態下では「善玉」としての作用が失われ、「機能不全HDL」となる。HDLの重要性は、量のみならず、質も併せて評価すべきであると変遷しているにもかかわらず、いまだ確立されたHDL機能評価法がないこと自体がHDL研究の大きな障壁となっている。本研究成果は「機能不全HDL」を簡便かつ再現性をもって検出することを可能とし、動脈硬化性疾患のリスク指標としてのHDLの意義についてリアルワールド・エビデンスの構築に寄与することのみならず、HDL機能改善を標的とした創薬に強力な研究基盤技術を提供することが期待される。

Report

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

    (9 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Fibronectin-containing High-Density Lipoprotein is Associated with Cancer Cell Adhesion and Proliferation2020

    • Author(s)
      Eriko Hisamatsu, Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Takuya Iino, Tetsuya Hara, Hidekazu Tanaka, Seimi Satomi-Kobayashi, Tatsuro Ishida, Ken-Ichi Hirata
    • Journal Title

      Kobe J Med Sci .

      Volume: 66

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association of cholesterol uptake capacity, a novel indicator for HDL functionality, and coronary plaque properties: An optical coherence tomography-based observational study2020

    • Author(s)
      Oshita T、Toh R、Nagano Y、Kuroda K、Nagasawa Y、Harada A、Murakami K、Kiriyama M、Yoshikawa K、Miwa K、Kubo T、Iino T、Nagao M、Irino Y、Hara T、Shinohara M、Otake H、Shinke T、Nakajima K、Ishida T、Hirata Ken-ichi
    • Journal Title

      Clinica Chimica Acta

      Volume: 503 Pages: 136-144

    • DOI

      10.1016/j.cca.2020.01.001

    • NAID

      120006824021

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease2019

    • Author(s)
      Nagao Manabu、Miyashita Kazuya、Mori Kenta、Irino Yasuhiro、Toh Ryuji、Hara Tetsuya、Hirata Ken-ichi、Shinohara Masakazu、Nakajima Katsuyuki、Ishida Tatsuro
    • Journal Title

      Journal of Clinical Lipidology

      Volume: 13 Issue: 5 Pages: 839-846

    • DOI

      10.1016/j.jacl.2019.07.007

    • NAID

      120007002630

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired Cholesterol‐Uptake Capacity of HDL Might Promote Target‐Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation2019

    • Author(s)
      Nagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, Tahara N, Tsukiyama Y, Yanaka K, Yamamoto H, Nagasawa A, Onishi H, Sugizaki Y, Takeshige R, Harada A, Murakami K, Kiriyama M, Oshita T, Irino Y, Kawamori H, Ishida T, Toh R, Shinke T, Hirata KI.
    • Journal Title

      Journal of the American Heart Association

      Volume: 8 Issue: 9

    • DOI

      10.1161/jaha.119.011975

    • NAID

      120006733129

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Comparison of Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, and Cholesterol Efflux Capacity in Association with Coronary Plaque Properties2019

    • Author(s)
      Toshihiko Oshita, Ryuji Toh, Mitsumasa Okano, Koichi Watanabe, Yuichiro Nagano, Amane Harada, Katsuhiro Murakami, Seimi Kobayashi, Masakazu Shinohara, Tetsuya Hara, Yasuhiro Irino, Hiromasa Otake,Tatsuro Ishida, Ken-ichi Hirata.
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] HDL機能の新規評価法“Cholesteroluptakecapacity”とOCT解析によ る冠動脈プラーク病変性状の比較検討2018

    • Author(s)
      尾下寿彦、杜隆嗣、入野康宏、黒田浩史、永野雄一郎、長澤圭典、大竹寛雅、新家俊郎、石田達郎、平田健一
    • Organizer
      第55回 日本臨床分子医学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Understanding of HDL Cholesterol Efflux Capacity: Towards Clinical Application2018

    • Author(s)
      Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata
    • 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] Searching for modulating factor of cholesterol uptake capacity, a novel indicator for HDL functionality2018

    • Author(s)
      Toshihiko Oshita, Ryuji Toh,Mitsumasa Okano, Shigeyasu Tsuda, Koichi Watanabe, Seimi Kobayashi, Tetsuya Hara, Masakazu Shinohara, Yasuhiro Irino, Katsuhiro Murakami, Amane Harada, Tatsuro Ishida, Ken-ichi Hirata
    • 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] Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, Versus Cholesterol Efflux Capacity in Association with Coronary Plaque Lipid2018

    • Author(s)
      Toshihiko Oshita, Ryuji Toh, Mitsumasa Okano, Koichi Watanabe, Yuichiro Nagano, Amane Harada, Katsuhiro Murakami, Seimi Kobayashi, Masakazu Shinohara, Tetsuya Hara, Yasuhiro Irino, Hiromasa Otake,Tatsuro Ishida, Ken-ichi Hirata.
    • Organizer
      American Heart Association Scientific Sessions 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research

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

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