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Search for novel biomarkers of heart failure by comprehensive genetic analysis of autopsy heart

Research Project

Project/Area Number 18K07011
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionAkita University

Principal Investigator

Yoshida Makoto  秋田大学, 医学系研究科, 講師 (70637553)

Co-Investigator(Kenkyū-buntansha) 前田 大地  大阪大学, 医学系研究科, 特任教授(常勤) (30585500)
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: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords心不全 / 網羅的遺伝子発現解析 / RNA-seq / バイオマーカー / 心筋細胞 / 拡張型心筋症 / 遺伝子解析 / 心不全バイオマーカー / RNAシークエンス / 病理解剖 / 凍結心筋 / 網羅的遺伝子解析 / 心臓凍結標本 / マイクロRNAマイクロアレイ
Outline of Final Research Achievements

In this study, RNA-seq analysis was performed on 12 autopsy hearts including Control. From the comparison between the heart failure group and the control group, a total of 6286 genes whose expression were up-regulated or down-regulated were confirmed. Among them, genes encoding proteins found in heart failure such as ANP and CRP were confirmed. From this result, it was considered that the selected autopsy heart was consistent with the heart failure cases. Some genes were picked up, and verified by RT-PCR. The gene expression were confirmed same as the results of RNA-seq analysis. Among them, it was found that three catalytic subunits of NADPH oxidase, NOX1-5 and DUOX1, 2, were up-regulated. Currently, we are investigating the correlation between the NOX1 gene expression and the ejection fraction of the left ventricle, which is an index of heart failure.

Academic Significance and Societal Importance of the Research Achievements

世界全体で心不全に罹患している患者は多く、心不全治療は現在でも臨床現場におけるトピックの一つである。心不全の病態解明、治療への応用のためには心不全時心筋の分子生物学的解析が必要とされるが、心臓はその特殊性から網羅的遺伝子解析による知見の蓄積が非常に乏しい。本研究では心不全症例の剖検心で網羅的遺伝子発現解析を行い、心不全患者の心筋における遺伝子発現を明らかとした。その中から新規の心不全指標となりうる遺伝子が同定された。新たな心不全の指標となりうるかについてはさらなる解析が必要だが、心不全を早期で捉え、早期治療介入や治療ターゲット、創薬への応用として期待され、その社会的意義は大きいと考えられる。

Report

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

    (6 results)

All 2020

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Multiple ulcerations and perforation in the small intestine after steroid treatment in eosinophilic granulomatosis with polyangiitis: a case report and literature review2020

    • Author(s)
      Ito Yukinobu、Yoshida Makoto、Sugiyama Tatsuo、Masuda Hirotake、Mori Mitsuo、Kimura Noriyuki、Umakoshi Michinobu、Miyabe Ken、Kudo-Asabe Yukitsugu、Goto Akiteru
    • Journal Title

      Cardiovascular Pathology

      Volume: 47 Pages: 107193-107193

    • DOI

      10.1016/j.carpath.2019.107193

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Post-mortem Plasma Cell-Free DNA Sequencing: Proof-of-Concept Study for the "Liquid Autopsy".2020

    • Author(s)
      Ito Y, Yoshida M, Inoue T, Habuchi T, Ikoma S, Katoh H, Kato M, Shibata T, Ishikawa S, Yachida S, Goto A.
    • Journal Title

      Sci Rep

      Volume: 10(1) Issue: 1 Pages: 2120-2120

    • DOI

      10.1038/s41598-020-59193-y

    • NAID

      120007089050

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A case of Russell body gastritis with multifocal lesions2020

    • Author(s)
      Umakoshi Michinobu、Miyabe Ken、Ishii Hajime、Kudo-Asabe Yukitsugu、Ito Yukinobu、Yoshida Makoto、Maeda Daichi、Sageshima Masato、Goto Akiteru
    • Journal Title

      SAGE Open Medical Case Reports

      Volume: 8 Pages: 8-8

    • DOI

      10.1177/2050313x20923840

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] The Time Change of VEGFA Concentration Gradient Leads Neovasculature to Stair-like Groth2020

    • Author(s)
      Ito, Y., Minerva, D., Yoshida, M., Suzuki, T. and Goto, A.
    • Organizer
      Vascular Discovery 2020 Scientific Sessions
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The Time Change of VEGF-A Concentration gradient leads neovasculature to Stair-like Growth; Mathematical modeling2020

    • Author(s)
      Ito, Y., Minerva, D., Tasaki, S., Nakamura, N., Yoshida, M., Goto, A. and Suzuki, T.
    • Organizer
      SPS Core-to-Core Program “Establishing International Research Network of Mathematical Oncology”
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高度の右左シャントをともなう肺毛細血管拡張を呈した一剖検例2020

    • Author(s)
      吉田 誠
    • Organizer
      第109回日本病理学会総会
    • Related Report
      2020 Annual Research Report

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

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