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Significance of cell-free DNA in heart failure

Research Project

Project/Area Number 17K16018
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Cardiovascular medicine
Research InstitutionFukushima Medical University

Principal Investigator

Misaka Tomofumi  福島県立医科大学, 医学部, 助教 (50793080)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords心不全 / エピジェネティクス / メチル化 / セルフリーDNA / メチル化解析 / エピジェネティックス
Outline of Final Research Achievements

The pressure-overload heart model by transverse aortic contraction in mice was generated. Analysis was performed by using the hypertrophic hearts at 1 week and failing hearts at 4 week after surgery. After bisulfite-conversion of the DNA was conducted, DNA methylation analysis by real-time PCR by methylation and unmethylated specific primers showed there were no differences between these diseased hearts and normal hearts in CpG island in ATP2A2 and Dux4.
Next, cell-free DNA (cfDNA) were isolated from the serum samples of the patients with heart failure. Quantitative analysis of cfDNA by real-time PCR using LINE1 primer, levels of cfDNA were significantly increased in heart failure patients compared to the subject without heart failure. In the methylation analysis of cfDNA, due to the small amount of cfDNA, digital PCR would be needed to conduct further analysis of cfDNA methylation.

Academic Significance and Societal Importance of the Research Achievements

循環血中セルフリーDNAは主に悪性腫瘍において研究が行われているが、心臓、とくに心不全におけるその意義については明確ではない。本研究では、心不全患者では、心不全を有さない対象と比較して、セルフリーDNAの有意な増加を認めた。方法論としてさらなる検討が必要であるが、心不全の病態・重症度に応じた特異的なDNAメチル化を同定しその程度を評価し得れば、メチル化セルフリーDNAが新たなバイオマーカー・予後指標になる可能性があると考えられ、引き続き解析を進める予定である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (23 results)

All 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (17 results) (of which Int'l Joint Research: 11 results)

  • [Journal Article] Plasma levels of melatonin in dilated cardiomyopathy2019

    • Author(s)
      Misaka Tomofumi、Yoshihisa Akiomi、Yokokawa Tetsuro、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Sugimoto Koichi、Kunii Hiroyuki、Nakazato Kazuhiko、Takeishi Yasuchika
    • Journal Title

      Journal of Pineal Research

      Volume: 66 Issue: 4

    • DOI

      10.1111/jpi.12564

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Soluble neprilysin does not correlate with prognosis in pulmonary hypertension2019

    • Author(s)
      Yoshihisa Akiomi、Yokokawa Tetsuro、Misaka Tomofumi、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Sugimoto Koichi、Kunii Hiroyuki、Nakazato Kazuhiko、Takeishi Yasuchika
    • Journal Title

      ESC Heart Failure

      Volume: 6 Issue: 2 Pages: 291-296

    • DOI

      10.1002/ehf2.12404

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure2019

    • Author(s)
      Sato Yu、Yoshihisa Akiomi、Kimishima Yusuke、Kiko Takatoyo、Kanno Yuki、Yokokawa Tetsuro、Abe Satoshi、Misaka Tomofumi、Sato Takamasa、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Takeishi Yasuchika
    • Journal Title

      Journal of Cardiac Failure

      Volume: 25 Issue: 3 Pages: 195-203

    • DOI

      10.1016/j.cardfail.2019.01.007

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Multiple Biomarker Approach in Patients with Cardiac Sarcoidosis2018

    • Author(s)
      Kiko Takatoyo、Yoshihisa Akiomi、Kanno Yuki、Yokokawa Tetsuro、Abe Satoshi、Miyata-Tatsumi Makiko、Misaka Tomofumi、Oikawa Masayoshi、Kobayashi Atsushi、Ishida Takafumi、Takeishi Yasuchika
    • Journal Title

      International Heart Journal

      Volume: 59 Issue: 5 Pages: 996-1001

    • DOI

      10.1536/ihj.17-695

    • NAID

      130007490569

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2018-09-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Association of Serum Zinc Level With Prognosis in Patients With Heart Failure2018

    • Author(s)
      Yoshihisa Akiomi、Abe Satoshi、Kiko Takatoyo、Kimishima Yusuke、Sato Yu、Watanabe Shunsuke、Kanno Yuki、Miyata-Tatsumi Makiko、Misaka Tomofumi、Sato Takamasa、Suzuki Satoshi、Oikawa Masayoshi、Kobayashi Atsushi、Yamaki Takayoshi、Kunii Hiroyuki、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
    • Journal Title

      Journal of Cardiac Failure

      Volume: 24 Issue: 6 Pages: 375-383

    • DOI

      10.1016/j.cardfail.2018.02.011

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Associations between diabetes mellitus and pulmonary hypertension in chronic respiratory disease patients2018

    • Author(s)
      Takahashi Tomoko、Yoshihisa Akiomi、Sugimoto Koichi、Yokokawa Tetsuro、Misaka Tomofumi、Kaneshiro Takashi、Oikawa Masayoshi、Kobayashi Atsushi、Nakazato Kazuhiko、Ishida Takafumi、Takeishi Yasuchika
    • Journal Title

      PLOS ONE

      Volume: 13 Issue: 10 Pages: e0205008-e0205008

    • DOI

      10.1371/journal.pone.0205008

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Plasma levels of melatonin in dilated and hypertrophic cardiomyopathies2019

    • Author(s)
      Tomofumi Misaka, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Prognostic impact of restless legs syndrome on patients with heart failure2019

    • Author(s)
      三阪智史, 義久精臣, 一條靖洋, 喜古崇豊, 君島勇輔, 佐藤 悠, 菅野優紀, 滝口 舞, 横川哲朗, 阿部諭史, 佐藤崇匡, 及川雅啓, 小林 淳, 八巻尚洋, 國井浩行, 中里和彦, 石田隆史, 竹石恭知
    • Organizer
      第83回 日本循環器学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Cardio-protective role of FKBP8 during pressure overload by preventing accumulation of misfolded proteins and ER-associated apoptosis2018

    • Author(s)
      Tomofumi Misaka, Kinya Otsu, Yasuchika Takeishi
    • Organizer
      Cardiovascular and Metabolic Week 2018: International Society for Heart Research (ISHR), The 35th Annual Meeting of the Japanese Section
    • Related Report
      2018 Annual Research Report
  • [Presentation] Prognostic impact of restless legs syndrome on hospitalized heart failure patients.2018

    • Author(s)
      Tomofumi Misaka, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Plasma levels of melatonin in dilated and hypertrophic cardiomyopathies2018

    • Author(s)
      Tomofumi Misaka, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Change in left ventricular ejection fraction and its impact on prognosis in heart failure patients with mid-range ejection fraction2018

    • Author(s)
      Yusuke Kimishima, Akiomi Yoshihisa, Yasuhiro Ichijo, Yu Sato, Takatoyo Kiko, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of endothelin-1 stimulation in the expression of activin receptor-like kinase-1 (ALK-1) in human pulmonary arterial endothelial cells2018

    • Author(s)
      Koichi Sugimoto, Yusuke Kimishima, Tomofumi Misaka, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Cardiovascular and Metabolic Week 2018: International Society for Heart Research (ISHR), The 35th Annual Meeting of the Japanese Section
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characteristics and outcomes of recovered left ventricular ejection fraction in heart failure patients with reduced ejection fraction2018

    • Author(s)
      Yusuke Kimishima, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yu Sato, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characteristics and outcomes of worsening left ventricular ejection fraction in heart failure patients with preserved ejection fraction2018

    • Author(s)
      Masayoshi Oikawa, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Yuki Kanno, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of combined post capillary pulmonary hypertension based on upcoming diagnostic criteria on the prognosis of pulmonary hypertension due to left-sided heart disease2018

    • Author(s)
      Koichi Sugimoto, Akiomi Yoshihisa, Tetsuro Yokokawa, Tomofumi Misaka, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of diabetes mellitus on the prediction for pulmonary hypertension in the patients with chronic respiratory disease2018

    • Author(s)
      Koichi Sugimoto, Akiomi Yoshihisa, Tomoko Takahashi, Tetsuro Yokokawa, Tomofumi Misaka, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Low T3 syndrome is associated with high mortality and impaired exercise capacity in hospitalized patients with heart failure2018

    • Author(s)
      Yu Sato, Akiomi Yoshihisa, Yusuke Kimishima, Takatoyo Kiko, Yuki Kanno, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Prognostic impact of periodic leg movements during sleep on patients with heart failure2018

    • Author(s)
      Yuki Kanno, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Mai Takiguchi, Tetsuro Yokokawa, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Senescence marker protein 30 affects phosphorylation of endothelial nitric oxide synthase in hypoxia-induced pulmonary hypertension in mice2018

    • Author(s)
      Koichi Sugimoto, Akihiko Sato, Satoshi Suzuki, Tetsuro Yokokawa, Tomofumi Misaka, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Soluble neprilysin does not correlate with outcome in hypertrophic cardiomyopathy2018

    • Author(s)
      Tetsuro Yokokawa, Akiomi Yoshihisa, Yasuhiro Ichijo, Takatoyo Kiko, Yusuke Kimishima, Yu Sato, Mai Takiguchi, Satoshi Abe, Tomofumi Misaka, Takamasa Sato, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Takafumi Ishida, Yasuchika Takeishi
    • Organizer
      Scientific Sessions of American Heart Association 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] FKBP8 protects the heart from hemodynamic stress by preventing the accumulation of misfolded proteins and endoplasmic reticulum-associated apoptosis in mice2018

    • Author(s)
      Tomofumi Misaka, Kinya Otsu, Yasuchika Takeishi
    • Organizer
      第22回 日本心不全学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] FKBP8 protects the heart by preventing accumulation of misfolded protein and ER-associated apoptosis2018

    • Author(s)
      Tomofumi Misaka, Kinya Otsu, Yasuchika Takeishi
    • Organizer
      The 2nd JCS Council Forum on Basic Cardio Vascular Research
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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