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Clinical significance of cholesterol uptake capacity, a novel assay of high-density lipoprotein function, in coronary artery disease

Research Project

Project/Area Number 15K09121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionKobe University

Principal Investigator

Tatsuro Ishida  神戸大学, 医学研究科, 特命教授 (00379413)

Co-Investigator(Kenkyū-buntansha) 杜 隆嗣  神戸大学, 医学研究科, 特命准教授 (50379418)
平田 健一  神戸大学, 医学研究科, 教授 (20283880)
Co-Investigator(Renkei-kenkyūsha) SHINKE TOSHIRO  神戸大学, 医学部附属病院, 准教授 (60379419)
Research Collaborator SHINOHARA MASAKAZU  神戸大学, 大学院医学研究科, 准教授 (80437483)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords高比重リポ蛋白 / コレステロール逆転送 / 動脈硬化 / 冠動脈疾患 / 脂質異常症 / HDL / エイコサペンタエン酸 / コレステロール / 逆転送 / オメガ3系多価不飽和脂肪酸 / リポタンパク質 / 高比重リポタンパク質 / コレステロール引き抜き / 脂質代謝異常 / 循環器
Outline of Final Research Achievements

We established a new method to evaluate the efficiency of HDL-induced cholesterol efflux from macrophages “cholesterol uptake capacity (CUC)” using apoB-depleted serum, fluorescently labeled cholesterol, and immobilized anti-apolipoprotein A1 antibody. When we measured CUC in patients with coronary artery disease, CUC declined with myeloperoxidase-mediated oxidation of HDL, and correlated inversely with requirement of revascularization. Multivariable analysis adjusted for traditional coronary risk factors including HDL-C showed that only CUC remained significant. Furthermore, CUC was lower in patients with lipidic plaque than that in those without lipidic plaque, and inversely associated with the lipid index in these patients. CUC was also inversely associated with Macrophage grade. CUC is an alternative measure of HDL functionality and may be a substitute for cholesterol efflux capacity and applicable for assessing CVD risk.

Report

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

    (30 results)

All 2018 2017 2016 2015

All Journal Article (12 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (18 results) (of which Int'l Joint Research: 5 results,  Invited: 2 results)

  • [Journal Article] Eicosapentaenoic Acid-Enriched High-Density Lipoproteins Exhibit Anti-Atherogenic Properties2018

    • Author(s)
      6.Tanaka N, Irino Y, Shinohara M, Tsuda S, Mori T, Nagao M, Oshita T, Mori K, Hara T, Toh R, Ishida T, Hirata K
    • Journal Title

      Circulation Journal

      Volume: 82 Issue: 2 Pages: 596-601

    • DOI

      10.1253/circj.CJ-17-0294

    • NAID

      130006321869

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel mechanism of regulation of the 5-lipoxygenase/leukotriene B4 pathway by high-density lipoprotein in macrophages2017

    • Author(s)
      Tsuda Shigeyasu、Shinohara Masakazu、Oshita Toshihiko、Nagao Manabu、Tanaka Nobuaki、Mori Takeshige、Hara Tetsuya、Irino Yasuhiro、Toh Ryuji、Ishida Tatsuro、Hirata Ken-ichi
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12989-12989

    • DOI

      10.1038/s41598-017-13154-0

    • NAID

      120006373799

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High-density lipoprotein protects cardiomyocytes from oxidative stress via the PI3K/mTOR signaling pathway2017

    • Author(s)
      Nagao Manabu、Toh Ryuji、Irino Yasuhiro、Nakajima Hideto、Oshita Toshihiko、Tsuda Shigeyasu、Hara Tetsuya、Shinohara Masakazu、Ishida Tatsuro、Hirata Ken-ichi
    • Journal Title

      FEBS Open Bio

      Volume: 7 Issue: 9 Pages: 1402-1409

    • DOI

      10.1002/2211-5463.12279

    • NAID

      120006373788

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of serum trans fatty acids concentration on plaque vulnerability in patients with coronary artery disease: Assessment via optical coherence tomography2017

    • Author(s)
      Nagasawa Yoshinori、Shinke Toshiro、Toh Ryuji、Ishida Tatsuro、Otake Hiromasa、Takaya Tomofumi、Sugiyama Daisuke、Terashita Daisuke、Tahara Natsuko、Shinkura Yuto、Uzu Kenzo、Kashiwagi Daiji、Kuroda Koji、Nagano Yuichiro、Yamamoto Hiroyuki、Yanaka Kenichi、Tsukiyama Yoshiro、Hirata Ken-ichi
    • Journal Title

      Atherosclerosis

      Volume: 265 Pages: 312-317

    • DOI

      10.1016/j.atherosclerosis.2017.06.922

    • NAID

      120006377646

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cholesterol Uptake Capacity: A New Measure of High-Density Lipoprotein Functionality for Coronary Risk Assessment.2017

    • Author(s)
      Harada A, Toh R, Murakami K, Kiriyama M, Yoshikawa K, Miwa K, Kubo T, Irino Y, Tanaka N, Nishimura K, Ishida T, Hirata K.
    • Journal Title

      Journal of Applied Laboratory Medicine.

      Volume: in press

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Excessive intake of trans fatty acid accelerates atherosclerosis through promoting inflammation and oxidative stress in a mouse model of hyperlipidemia.2017

    • Author(s)
      Monguchi T, Hara T, Hasokawa M, Nakajima H, Mori K, Toh R, Irino Y, Ishida T, Hirata KI, Shinohara M
    • Journal Title

      J Cardiol

      Volume: 印刷中 Issue: 2 Pages: 121-127

    • DOI

      10.1016/j.jjcc.2016.12.012

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced Impact of Cholesterol Absorption Marker on New Atherosclerotic Lesion Progression After Coronary Intervention During Statin Therapy2017

    • Author(s)
      Mori K, Ishida T, Tsuda S, Oshita T, Shinohara M, Hara T, Irino Y, Toh R, Hirata KI.
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 24 Issue: 2 Pages: 123-132

    • DOI

      10.5551/jat.32615

    • NAID

      130005306526

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] HDLの抗炎症能の分子機序と評価方法2016

    • Author(s)
      田中伸明,石田達郎.
    • Journal Title

      臨床病理

      Volume: 64 Pages: 49-56

    • Related Report
      2016 Research-status Report
  • [Journal Article] 高HDL-C血症2016

    • Author(s)
      篠原正和, 石田達郎
    • Journal Title

      Medical Practice

      Volume: 33 Pages: 575-580

    • Related Report
      2015 Research-status Report
  • [Journal Article] HDLの抗炎症能の分子機序と評価方法.2016

    • Author(s)
      田中伸明、石田達郎
    • Journal Title

      臨床病理

      Volume: 64 Pages: 49-56

    • Related Report
      2015 Research-status Report
  • [Journal Article] 家族性低HDLコレステロール血症の分子機構2015

    • Author(s)
      原哲也, 石田達郎
    • Journal Title

      臨床病理.

      Volume: 33 Pages: 57-60

    • Related Report
      2015 Research-status Report
  • [Journal Article] LDL/HDLコレステロールを標的とした動脈硬化症の新しい治療ストラテジー. 機能不全HDLに対する治療戦略.2015

    • Author(s)
      入野康宏, 石田達郎, 杜隆嗣.
    • Journal Title

      血管医学

      Volume: 16 Pages: 53-60

    • Related Report
      2015 Research-status Report
  • [Presentation] Identification of Determinants of Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality2018

    • Author(s)
      Oshita T, Toh R, Ishida T, et al.
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Relationships between Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, and Morphologic Features of Coronary Plaque2018

    • Author(s)
      Oshita T, Toh R, Ishida T, et al.
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Phospholipid Composition of Reconstitute High Density Lipoproteins Affects their Anti-inflammatory Effects2018

    • Author(s)
      Okano M, Irino Y, Ishida T, et al.
    • Organizer
      第82回日本循環器学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Inverse Association Between HDL Cholesterol Uptake Capacity And Coronary Atherosclerotic Burden: OCT-based Observation Study2017

    • Author(s)
      Toshihiko Oshita, Ryuji Toh, Amane Harada, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Keiko Miwa, Kenta Mori, Yasuhiro Irino, Hiromasa Otake, Toshiro Shinke, Tatsuro Ishida, Ken-ichi Hirata
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinical and Practical Assessment of Dysfunctional HDL in Cardiovascular Risk Stratification2017

    • Author(s)
      Tatsuro Ishida, Ryuji Toh, Hiromasa Otake, Toshiro Shinke, Amane Harada, Ken-ichi Hirata
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Impaired HDL-cholesterol uptake capacity which measure HDL functionality may associate with target lesion revascularization through provoking neoatherosclerosis formation after stenting2017

    • Author(s)
      永野雄一朗、大竹寛雅 、入野 康宏、鳥羽 敬義、高橋 八大 、寺下大輔 、黒田浩史、宇津賢三、田原奈津子 、新倉悠人、長澤圭典、築山義朗、谷仲謙一、山本裕之、新家俊郎、原田周、村上克洋、石田達郎、杜隆嗣、平田健一
    • Organizer
      第81回 日本循環器学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2017-03-17
    • Related Report
      2016 Research-status Report
  • [Presentation] Association of Coronary Lipidic Plaque Burden with Impairment of Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality: OCT-based Observation Study2017

    • Author(s)
      Oshita T, Toh R, Ishida T, et al.
    • Organizer
      American Heart Association Scientific sessions 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Mechanism of High-Density Lipoprotein to Regulate 5-Lipoxygenase/Leukotriene B4 Pathway in Macrophages2017

    • Author(s)
      Tsuda S, Ishida T, et al.
    • Organizer
      American Heart Association Scientific sessions 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cholesterol Uptake Capacity: A New Measure of HDL Functionality for Coronary Risk Stratification2016

    • Author(s)
      Amane Harada, Ryuji Toh, Katsuhiro Murakami, Maria Kiriyama, Keiko Yoshikawa, Keiko Miwa, Takuya Kubo, Yasuhiro Irino, Kenta Mori, Nobuaki Tanaka, Kunihiro Nishimura, Tatsuro Ishida, Ken-ichi Hirata
    • Organizer
      第33回 ISHR日本部会総会
    • Place of Presentation
      東京
    • Year and Date
      2016-12-16
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] HDL粒子によるコレステロール引抜き/取込み能と冠動脈疾患との関係2016

    • Author(s)
      Toh R,, Ishida T,Harada A, Yoshida T, Hirata K.
    • Organizer
      第64回日本心臓病学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Cholesterol uptake capacity, a new concept of HDL functionality, for risk stratification in coronary artery disease2016

    • Author(s)
      Toh R, Harada A, Murakami K, Kiriyama M, Yoshikawa K, Miwa K, Irino Y, Mori K, Tanaka N, Nishimura K, Ishida T, Hirata K.
    • Organizer
      68th AACC Annual Scientific Meeting & Clinical Lab Expo
    • Place of Presentation
      Philadelphia, USA
    • Year and Date
      2016-08-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高比重リポ蛋白 (HDL) の抗炎症効果はリン脂質構成に依存する2016

    • Author(s)
      Tanaka N, Irino Y, Shinohara M, Tsuda S, Nagao M, Mori K, Mori T, Hara T, Toh R, Ishida T, Hirata K.
    • 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
      2016 Research-status Report
  • [Presentation] Cholesterol Uptake Capacity, a New Measure for High-Density Lipoprotein Functionality And Its Association with Incident Cardiovascular Events.2016

    • Author(s)
      Harada A, Toh R, Murakami K, Kiriyama M, Yoshikawa K, Kubo T, Miwa K, Irino Y, Mori K, Tanaka N, Ishida T, Hirata K.
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] High-Density Lipoproteins from Coronary Artery Disease Patients Contribute to Inflammatory-prone Lipid Mediator Production.2016

    • Author(s)
      Tsuda S, Shinohara M, Irino Y, Mori K, Tanaka N, Ishida T, Hirata K.
    • Organizer
      第80回日本循環器学会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] HDLの抗炎症能・コレステロール引抜き能の評価方法の確立と動脈硬化における意義2016

    • Author(s)
      Ishida T
    • Organizer
      第48回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Serum Myeloperoxidase/Paraoxonase 1 Ratio Predicts Recurrent Coronary Artery Disease2015

    • Author(s)
      Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
    • Organizer
      第47回 日本動脈硬化学会総会学術集会
    • Place of Presentation
      仙台
    • Year and Date
      2015-07-10
    • Related Report
      2015 Research-status Report
  • [Presentation] 冠動脈疾患二次予防における予測因子としての血清ミエロペルオキシダーゼ/パラオキソナーゼ1比の有用性についての検討2015

    • Author(s)
      Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
    • Organizer
      第15回日本NO学会
    • Place of Presentation
      大阪
    • Year and Date
      2015-06-26
    • Related Report
      2015 Research-status Report
  • [Presentation] Serum myeloperoxidase/paraoxonase 1 ration predicts recurrent coronary artery disease2015

    • Author(s)
      Tsuda S, Toh R, Mori K, Nagao M, Tanaka N, Mori T, Monguchi T, Nakajima H, Honjo T, Shinohara M, Nishimura K, Ishida T, Hirata K
    • Organizer
      ATVB/PVD2015
    • Place of Presentation
      サンフランシスコ、アメリカ
    • Year and Date
      2015-05-08
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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

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