Significance of cell-free DNA in heart failure

2018 Fiscal Year Annual Research Report

• Project/Area Number: 17K16018
• Research Institution: Fukushima Medical University
• Principal Investigator: 三阪 智史 福島県立医科大学, 医学部, 助教 (50793080)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: セルフリーDNA / メチル化解析 / 心不全

Outline of Annual Research Achievements

昨年度に引き続き、マウス心不全モデルにおけるDNAメチル化解析と、ヒトセルフリーDNAのメチル化解析を行った。
C57BL/6J野生型マウスに大動脈縮窄(Transverse Aortic Constriction, TAC)による圧負荷モデルを作成した。TAC1週後の心肥大期および4週後の心不全非代償期のモデルを用いて、DNAおよびRNAを抽出した。過去の報告およびデータベースからDNAメチル化で制御される遺伝子をターゲットに、RT-qPCRによる遺伝子発現解析およびメチル化・非メチル化特異的プライマーを用いて、DNAメチル化の程度について評価を行った。遺伝子発現と関連するプロモーター領域のCpGアイランドにおいて、DNAメチル化解析を行った。。
健常者および患者血液から専用スピッツを用いて、血液を採取した。遠心後、血清中よりセルフリーDNAを抽出し、セルフリーDNAの定量を行った。セルフリーDNAの抽出方法のoptimizationに難渋したが、安定したセルフリーDNAの抽出が出来ることを確認した上で、コントロールとしての健常人と、心不全患者における循環血中セルフリーDNAを比較検討した。LINEのプライマーを用いた定量的PCR法により、心不全患者でセルフリーDNAが増加していることが明らかになった。さらに、そのセルフリーDNAをバイサルファイト処理を行い、メチル化解析へと進めた。メチル化特異的プライマーを設計して、その解析を行った。

Research Products

• [Journal Article] Plasma levels of melatonin in dilated cardiomyopathy (2019)
  • 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 Pages: e12564～e12564
  • DOI: doi: 10.1111/jpi.12564
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Soluble neprilysin does not correlate with prognosis in pulmonary hypertension (2019)
  • 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 Pages: 291～296
  • DOI: doi: 10.1002/ehf2.12404
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Low T3 Syndrome Is Associated With High Mortality in Hospitalized Patients With Heart Failure (2019)
  • 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 Pages: 195～203
  • DOI: doi: 10.1016/j.cardfail.2019.01.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of Serum Zinc Level With Prognosis in Patients With Heart Failure (2018)
  • 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 Pages: 375～383
  • DOI: doi: 10.1016/j.cardfail.2018.02.011
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Multiple Biomarker Approach in Patients with Cardiac Sarcoidosis (2018)
  • 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 Pages: 996～1001
  • DOI: doi: 10.1536/ihj.17-695
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Associations between diabetes mellitus and pulmonary hypertension in chronic respiratory disease patients (2018)
  • 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 Pages: e0205008
  • DOI: 10.1371/journal.pone.0205008
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Plasma levels of melatonin in dilated and hypertrophic cardiomyopathies (2019)
  • 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
• [Presentation] Prognostic impact of restless legs syndrome on patients with heart failure (2019)
  • 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
• [Presentation] Cardio-protective role of FKBP8 during pressure overload by preventing accumulation of misfolded proteins and ER-associated apoptosis (2018)
  • 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
• [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
  • Int'l Joint Research
• [Presentation] Plasma levels of melatonin in dilated and hypertrophic cardiomyopathies (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
  • Int'l Joint Research
• [Presentation] Change in left ventricular ejection fraction and its impact on prognosis in heart failure patients with mid-range ejection fraction (2018)
  • 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
  • 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 cells (2018)
  • 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
• [Presentation] Characteristics and outcomes of recovered left ventricular ejection fraction in heart failure patients with reduced ejection fraction (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Characteristics and outcomes of worsening left ventricular ejection fraction in heart failure patients with preserved ejection fraction (2018)
  • 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
  • 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 disease (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Impact of diabetes mellitus on the prediction for pulmonary hypertension in the patients with chronic respiratory disease (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Low T3 syndrome is associated with high mortality and impaired exercise capacity in hospitalized patients with heart failure (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Prognostic impact of periodic leg movements during sleep on patients with heart failure (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Senescence marker protein 30 affects phosphorylation of endothelial nitric oxide synthase in hypoxia-induced pulmonary hypertension in mice (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Soluble neprilysin does not correlate with outcome in hypertrophic cardiomyopathy (2018)
  • 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
  • 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 mice (2018)
  • Author(s): Tomofumi Misaka, Kinya Otsu, Yasuchika Takeishi
  • Organizer: 第22回 日本心不全学会学術集会
• [Presentation] FKBP8 protects the heart by preventing accumulation of misfolded protein and ER-associated apoptosis (2018)
  • Author(s): Tomofumi Misaka, Kinya Otsu, Yasuchika Takeishi
  • Organizer: The 2nd JCS Council Forum on Basic Cardio Vascular Research