A New Diagnostics Method for Refractory Heart Failure

• Project/Area Number: 24591097
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: ASANO YOSHIHIRO 大阪大学, 医学(系)研究科(研究院), 助教 (60527670)
• Co-Investigator(Kenkyū-buntansha): HIGO Shuichiro 大阪大学, 医学(系)研究科(研究院), 助教 (00604034) ; TSUKAMOTO Osamu 大阪大学, 医学(系)研究科(研究院), 助教 (80589151) ; MINAMINO Tetsuo 大阪大学, 医学(系)研究科(研究院), 准教授 (30379234) ; KATO Hisakazu 大阪大学, 医学(系)研究科(研究院), 特任研究員 (30589312) ; OGITA Hisakazu 滋賀医科大学, 医学部, 教授 (50379236) ; SANADA Shoji 大阪大学, 医学(系)研究科(研究院), 助教 (70593797)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: エピゲノム / 細胞核クロマチン / 難治性心不全 / 分子循環器病学 / 臨床循環器

Outline of Final Research Achievements

Higher order structures in the cell nucleus have been demonstrated to change during development and differentiation. Such structural remodeling occurred in the cell nucleus can be observed as changes in high electron density areas called chromatin by electron microscopy. Alterations in nuclear chromatin structure have been reported some relation with physiological changes. Based on our experimental findings of chromatin remodeling as an upstream of pathological gene expression in cardiomyocytes, we focused on changes in nuclear chromatin structure of cardiomyocytes in patients with dilated cardiomyopathy (DCM). Using our original quantitation methods to analyze the ultrastructure of chromatin, we conducted a retrospective observational study assessing the ability to identify the DCM patients with severe heart failure at risk for poor outcomes, and to make an accurate and an early determination of the indication for some ventricular assist devices to support the failing heart.

Research Products

• [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase (2015)
  • Author(s): T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
  • Journal Title: Proc. Nat. Acad. Sci. U.S.A. Volume: 112 Issue: 5 Pages: 1553-1558
  • DOI: 10.1073/pnas.1419767112
  • Peer Reviewed / Open Access
• [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5. (2015)
  • Author(s): Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 6137-6137
  • DOI: 10.1038/ncomms7137
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart. (2014)
  • Author(s): Matsuoka K, Asano Y, Higo S, Tsukamoto O, Yan Y, Yamazaki S, Matsuzaki T, Kioka H, Kato H, Uno Y, Asakura M, Asanuma H, Minamino T, Aburatani H, Kitakaze M, Komuro I, Takashima S.
  • Journal Title: FASEB J. Volume: 28(4) Issue: 4 Pages: 1870-9
  • DOI: 10.1096/fj.13-245522
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: Role of NO. (2014)
  • Author(s): Asanuma H, Sanada S, Asakura M, Asano Y, Kim J, Shinozaki Y, Mori H, Minamino T, Takashima S,Kitakaze M.
  • Journal Title: Hypertens Res. Volume: 37(8) Issue: 8 Pages: 716-23
  • DOI: 10.1038/hr.2014.70
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Comprehensive metagenomic approach for detecting causative microorganisms in culture-negative infective endocarditis. (2014)
  • Author(s): Imai A, Gotoh K, Asano Y* (corresponding author), Yamada N, Motooka D, Fukushima M, Kanzaki M, Ohtani T, Sakata Y, Nishi H, Toda K, Sawa Y, Komuro I, Horii T, Iida T, Nakamura S, Takashima S.
  • Journal Title: Int J Cardiol. Volume: 172 Issue: 2 Pages: 288-9
  • DOI: 10.1016/j.ijcard.2013.12.197
  • Peer Reviewed
• [Journal Article] Usefulness of transient elastography for noninvasive and reliable estimation of right-sided filling pressure in heart failure. (2014)
  • Author(s): Taniguchi T, Sakata Y, Ohtani T, Mizote I, Takeda Y, Asano Y, Masuda M, Minamiguchi H, Kanzaki M, Ichibori Y, Nishi H, Toda K, Sawa Y, Komuro I.
  • Journal Title: Am J Cardiol. Volume: 113 Issue: 3 Pages: 552-8
  • DOI: 10.1016/j.amjcard.2013.10.018
  • Peer Reviewed
• [Journal Article] Low admission heart rate is a marker rather than a mediator of increased in-hospital mortality for patients with acute heart failure syndromes in sinus rhythm. (2014)
  • Author(s): Kajimoto K, Sato N, et al.
  • Journal Title: Int J Cardiol. Volume: 171 Issue: 1 Pages: 98-100
  • DOI: 10.1016/j.ijcard.2013.11.087
  • Peer Reviewed
• [Journal Article] Evaluation of intra-mitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation (2013)
  • Author(s): Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Tkafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y and Takashima S
  • Journal Title: PNAS Volume: 111 Issue: 1 Pages: 273-278
  • DOI: 10.1073/pnas.1318547111
  • Peer Reviewed / Open Access
• [Journal Article] Dipeptidyl-peptidase IV inhibition improves pathophysiology of heart failure and increases survival rate in pressure-overloaded mice. (2013)
  • Author(s): Takahashi A, Asakura M, Ito S, Min KD, Shindo K, Yan Y, Liao Y, Yamazaki S, Sanada S, Asano Y, Ishibashi-Ueda H, Takashima S, Minamino T, Asanuma H, Mochizuki N, Kitakaze M
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 304(10) Issue: 10 Pages: H1361-H1369
  • DOI: 10.1152/ajpheart.00454.2012
  • Peer Reviewed
• [Journal Article] Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model. (2013)
  • Author(s): Takahama H, Shigematsu H, Asai T, Matsuzaki T, Sanada S, Fu HY, Okuda K, Yamato M, Asanuma H, Asano Y, Asakura M, Oku N, Komuro I, Kitakaze M, Minamino T.
  • Journal Title: Cardiovasc Drugs Ther. Volume: 27 Issue: 2 Pages: 125-132
  • DOI: 10.1007/s10557-012-6437-6
  • Peer Reviewed
• [Journal Article] Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension. (2013)
  • Author(s): Taniguchi T, Ohtani T, Mizote I, Kanzaki M, Ichibori Y, Minamiguchi H, Asano Y, Sakata Y, Komuro I.
  • Journal Title: J Cardiol. Volume: 61 Issue: 6 Pages: 417-22
  • DOI: 10.1016/j.jjcc.2013.01.009
  • Peer Reviewed
• [Journal Article] Hyponatremia and in-hospital mortality in patients admitted for heart failure (from the ATTEND registry). (2013)
  • Author(s): Sato N, Gheorghiade M, Kajimoto K, Munakata R, Minami Y, Mizuno M, Aokage T, Asai K, Sakata Y, Yumino D, Mizuno K, Takano T; ATTEND Investigators.
  • Journal Title: Am J Cardiol. Volume: 111 Issue: 7 Pages: 1019-25
  • DOI: 10.1016/j.amjcard.2012.12.019
  • Peer Reviewed
• [Journal Article] Relationship between systolic blood pressure and preserved or reduced ejection fraction at admission in patients hospitalized for acute heart failure syndromes. (2013)
  • Author(s): Kajimoto K, Sato N, Sakata Y, Takano T; Acute Decompensated Heart Failure Syndromes (ATTEND) investigators.
  • Journal Title: Int J Cardiol. Volume: 168 Issue: 5 Pages: 4790-5
  • DOI: 10.1016/j.ijcard.2013.07.226
  • Peer Reviewed
• [Journal Article] H(2) mediates cardioprotection via involvements of K(ATP) channels and permeability transition pores of mitochondria in dogs. (2012)
  • Author(s): Yoshida A, Asanuma H, Sasaki H, Sanada S, Yamazaki S, Asano Y, Shinozaki Y, Mori H, Shimouchi A, Sano M, Asakura M, Minamino T, Takashima S, Sugimachi M, Mochizuki N, Kitakaze M.
  • Journal Title: Cardiovasc Drugs Ther. Volume: 26 Pages: 217-26
  • Peer Reviewed
• [Presentation] 拡張型心筋症の病態不可逆性を予測する新規心臓エピゲノム診断指標の開発 (2015)
  • Author(s): 朝野仁裕
  • Organizer: 第44回日本心脈管作動物質学会
  • Place of Presentation: 高松
  • Year and Date: 2015-02-06 – 2015-02-07
  • Invited
• [Presentation] A New Diagnostics Method for Refractory Heart Failure (2015)
  • Author(s): 朝野仁裕
  • Organizer: 第31回国際心臓研究学会（ISHR）日本部会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-01-10 – 2015-01-11
  • Invited
• [Presentation] 重症慢性心不全の病態可塑性判断を可能にする心臓病理エピゲノム診断指標の開発 (2014)
  • Author(s): 朝野仁裕
  • Organizer: 第62回日本心臓病学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-26 – 2014-09-27
  • Invited
• [Presentation] G0/G1 Switch Gene 2 Promotes Mitochondrial ATP Production and Protects Cardiomyocytes from the Energy Crisis under Hypoxia (2013)
  • Author(s): Hidetaka Kioka, Yoshihiro Asano, Seiji Takashima, Masafumi Kitakaze, Issei Komuro
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
• [Presentation] Quantitative ChIP-Sequence Analysis Reveals the Differentially Altered Active Epigenomic States in Murine Pressure-Overloaded Failing Hearts (2012)
  • Author(s): Higo Shuichiro, Asano Yoshihiro, Takashima Seiji, Kitakaze Masafumi, Komuro Issei
  • Organizer: The 29th Annual Meeting of the International Society for Heart Research Japanese Section
  • Place of Presentation: Fukuoka
• [Presentation] 「パネルディスカッション 再生医療に貢献する技術」 心筋細胞の可塑性を判断する病理学的臨床指標の開発 (2012)
  • Author(s): 朝野 仁裕
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] 心筋細胞核クロマチン形態は拡張型心筋症患者の予後不良予測因子となりうる
  • Author(s): 神崎万智子、朝野仁裕
  • Organizer: 第35 回心筋生検研究会
  • Place of Presentation: 東京
• [Presentation] Heart Failure Specific Enhancer Regulates the Expression of Natriuretic Peptides
  • Author(s): Ken Matsuoka, Yoshihiro Asano
  • Organizer: 第17 回日本心不全学会学術集会
  • Place of Presentation: 埼玉大宮
• [Presentation] Morphometric and Quantitative Analysis in Cardiomyocyte’s Nucleus were Associated with Poor Outcome in Patients with Idiopathic Dilated Cardiomyopathy
  • Author(s): Machiko Kanzaki, Yoshihiro Asano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Research Strategies of Whole Exome Sequencing ~ Practical Approaches for 110 Patients (32 families) with Hereditary Cardiomyopathy and Arrhythmia ~
  • Author(s): Yoshihiro Asano
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] Comprehensive quantitative epigenome mapping reveals the differential induction of histone H3 lysine 4 trimethylation marks in pressure-overloaded murine hearts
  • Author(s): Shuichiro Higo,Yoshihiro Asano, Seiji Takashima, Masafumi Kitakaze, Issei Komuro
  • Organizer: American Heart Association Scientific Sessions 2012
  • Place of Presentation: Los Angeles、USA
• [Book] 循環器専門医 (2015)
  • Author(s): 朝野仁裕
  • Publisher: 南光堂
• [Book] 循環器内科 (2015)
  • Author(s): 朝野仁裕
  • Publisher: 科学評論社
• [Book] 医学のあゆみ (2013)
  • Author(s): 朝野仁裕、小室一成.
  • Publisher: 医歯薬出版株式会社
• [Book] 週刊『医学のあゆみ』第一土曜日特集 特集「エクソーム解析―成果と将来」 「全エクソーム解析による難治性循環器疾患の原因遺伝子の同定」 (2013)
  • Author(s): 朝野仁裕、小室一成
  • Publisher: 医歯薬出版株式会社
• [Book] メディカルサイエンス病態生化学／臨床化学検査学II 病態の生化学－人体の正常と異常 II-2 臓器機能の生化学 II-2-3 心・循環器機能 (2013)
  • Author(s): 朝野仁裕、小室一成
  • Publisher: 近代出版
• [Book] 診断と治療 特集 心不全 最近の話題 心不全の原因診断の進歩 (2012)
  • Author(s): 朝野仁裕、小室一成
  • Publisher: 診断と治療社
• [Patent(Industrial Property Rights)] 心不全の重症度を無侵襲で経時的に正確に定量評価可能なマウス (2013)
  • Inventor(s): 高島成二, 朝野仁裕, 松岡研, 塚本蔵, 北風政史
  • Industrial Property Rights Holder: 高島成二, 朝野仁裕, 松岡研, 塚本蔵, 北風政史
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-228824
  • Filing Date: 2013-09-02