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Elucidating molecular mechanisms of HDL functionality

Research Project

Project/Area Number 18K08072
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

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

Co-Investigator(Kenkyū-buntansha) 入野 康宏  神戸大学, 医学研究科, 医学研究員 (10415565)
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高比重リポたんぱく質(HDL) / 高比重リポ蛋白(HDL) / フィブロネクチン / がん / 高比重リポタンパク質 / 高密度リポタンパク質
Outline of Final Research Achievements

A large amount of evidence suggests that high-density lipoprotein (HDL) has anti- atherosclerotic properties. HDL-cholesterol (HDL-C) has also been widely used as a marker of cardiovascular disease. Recently, it was reported that plasma HDL-C levels are inversely correlated with cancer risk. However, the relationship between HDL and cancer pathophysiology remains unknown.
We focused on fibronectin, an essential extracellular matrix glycoprotein, as an HDL-associated protein. Our study showed the possible mechanism by which fibronectin-containing HDL enhanced cancer cell proliferation and adhesion via the focal adhesion kinase signaling pathway. Further investigation of the roles of HDL components in tumorigenesis might provide novel insight into cancer pathophysiology.

Academic Significance and Societal Importance of the Research Achievements

近年、HDL機能が心血管疾患のリスク因子として注目を集めている。炎症を基盤とする病態ではHDL構成脂質組成が変化したり、化学的修飾を受けたりすることで、HDLの機能は低下しているがその分子機序は不明な点が多い。本研究成果は、HDL機能がどのような要因・メカニズムで影響されているかについての解明へとつながることが期待される。
一方、動脈硬化性疾患のみならず癌領域でもリポ蛋白質の代謝障害と種々の臓器の発癌との関連が示唆されているが、本研究では含有する分子によってHDLは癌の発生・進展に対しむしろ負の方向に働く可能性を示し、新たな診断・治療戦略に貢献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

    (15 results)

All 2020 2019 2018

All Journal Article (11 results) (of which Peer Reviewed: 11 results,  Open Access: 4 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (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

    • NAID

      120006975804

    • 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] A Novel Indicator for HDL Functionality2019

    • Author(s)
      Irino Yasuhiro、Toh Ryuji、Ishida Tatsuro
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 26 Issue: 11 Pages: 945-946

    • DOI

      10.5551/jat.ED111

    • NAID

      130007740418

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2019-11-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Elevated Serum Elaidic Acid Predicts Risk of Repeat Revascularization After Percutaneous Coronary Intervention in Japan2019

    • Author(s)
      Oshita Toshihiko、Toh Ryuji、Shinohara Masakazu、Mori Kenta、Irino Yasuhiro、Nagao Manabu、Hara Tetsuya、Otake Hiromasa、Ishida Tatsuro、Hirata Ken-ichi
    • Journal Title

      Circulation Journal

      Volume: 83 Issue: 5 Pages: 1032-1038

    • DOI

      10.1253/circj.CJ-18-1175

    • NAID

      130007636975

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-04-25
    • Related Report
      2018 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] Effect of rosuvastatin and eicosapentaenoic acid on neoatherosclerosis: the LINK-IT Trial2019

    • Author(s)
      Kuroda K, Otake H, Shinohara M, Kuroda M, Tsuda S, Toba T, Nagano Y, Toh R, Ishida T, Shinke T, Hirata KI.
    • Journal Title

      EuroIntervention

      Volume: 15 Issue: 12 Pages: e1099-e1106

    • DOI

      10.4244/eij-d-18-01073

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [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
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of novel serum markers for the progression of coronary atherosclerosis in WHHLMI rabbits, an animal model of familial hypercholesterolemia2019

    • Author(s)
      Shiomi Masashi、Takeda Hiroaki、Irino Yasuhiro、Kimura Norie、Yamada Satoshi、Kuniyoshi Nobue、Kikumori Akio、Koike Yu、Koike Tomonari、Yoshida Masaru、Izumi Yoshihiro、Shinohara Masakazu、Bamba Takeshi、Ishida Tatsuro
    • Journal Title

      Atherosclerosis

      Volume: 284 Pages: 18-23

    • DOI

      10.1016/j.atherosclerosis.2019.02.020

    • NAID

      120006850489

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Species differences in lipoprotein lipase and hepatic lipase activities: comparative studies of animal models of lifestyle-related diseases2019

    • Author(s)
      KIMURA Norie、KIKUMORI Akio、KAWASE Daisuke、OKANO Mitsumasa、FUKAMACHI Kumiko、ISHIDA Tatsuro、NAKAJIMA Katsuyuki、SHIOMI Masashi
    • Journal Title

      Experimental Animals

      Volume: 68 Issue: 3 Pages: 267-275

    • DOI

      10.1538/expanim.18-0176

    • NAID

      130007689907

    • ISSN
      0007-5124, 1341-1357, 1881-7122
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cardioprotective Effects of High-Density Lipoprotein Beyond its Anti-Atherogenic Action2018

    • Author(s)
      Nagao Manabu、Nakajima Hideto、Toh Ryuji、Hirata Ken-ichi、Ishida Tatsuro
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 25 Issue: 10 Pages: 985-993

    • DOI

      10.5551/jat.RV17025

    • NAID

      130007493050

    • ISSN
      1340-3478, 1880-3873
    • Year and Date
      2018-10-01
    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impact of serum cholesterol esterification rates on the development of diabetes mellitus in a general population2018

    • Author(s)
      Tanaka Shin-ichiro、Fujioka Yoshio、Tsujino Takeshi、Ishida Tatsuro、Hirata Ken-ichi
    • Journal Title

      Lipids in Health and Disease

      Volume: 17 Issue: 1

    • DOI

      10.1186/s12944-018-0822-5

    • NAID

      120006496807

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, Versus Cholesterol Efflux Capacity in Association with Coronary Plaque Lipid Burden2018

    • 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
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [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] 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
  • [Book] 心血管病イベントと脂質リスク管理. In: 熱血循環器学2019

    • Author(s)
      杜 隆嗣、石田 達郎、
    • Total Pages
      17
    • Publisher
      洋學社
    • Related Report
      2018 Research-status Report

URL: 

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

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