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2013 Fiscal Year Final Research Report

Elucidation of transcriptional and epigenomic regulation in the development of heart failure

Research Project

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Project/Area Number 23390210
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKyoto University

Principal Investigator

KUWAHARA Koichiro  京都大学, 医学(系)研究科(研究院), 講師 (30402887)

Co-Investigator(Kenkyū-buntansha) NISHIKIMI Toshio  京都大学, 大学院・医学研究科, 准教授 (80291946)
NAKAGAWA Yasuaki  京都大学, 大学院・医学研究科, 助教 (70452357)
KINOSHITA Hideyuki  京都大学, 大学院・医学研究科, 助教 (30467477)
Co-Investigator(Renkei-kenkyūsha) TAKANO Makoto  自治医科大学, 医学部, 教授 (30236252)
ARAI Yuji  独立行政法人国立循環器病研究センター, 分子生物学部, 室長 (30202724)
MORI Yasuo  京都大学, 工学研究科, 教授 (80212265)
NISHIDA Motohiro  九州大学, 薬学研究科, 准教授 (90342641)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywords転写調節 / 心不全
Research Abstract

We examined the transcriptional and epigenomic regulation of cardiac gene expression during the development of heart failure. We found that NRSF-HDAC complex maintains cardiac electrostability by regulating HCN2 and 4 ion channels expression. In addition, we revealed the important role played by MRTF-A, a rho-dependent co-activator of SRF, in pathological cardiac remodeling. Furthermore, we analyzed the therapeutic effect of TRPC3/6 inhibition on pathological cardiac remodeling.

  • Research Products

    (46 results)

All 2014 2013 2012 2011 Other

All Journal Article (22 results) Presentation (19 results) Book (4 results) Remarks (1 results)

  • [Journal Article] The Effects of Super-Flux (High Performance) Dialyzer on Plasma Glycosylated Pro-B-Type Natriuretic Peptide (proBNP) and Glycosylated N-Terminal proBNP in End-Stage Renal Disease Patients on Dialysis2014

    • Author(s)
      Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Minami T, Yamada C, Ueshima K, Ikeda Y, Okamoto H, Horii K, Nagata K, Kangawa K, Minamino N, Nakao K
    • Journal Title

      PLoS One

      Volume: 9(3) Pages: e92314

  • [Journal Article] Identification of Chemicals Inducing Cardiomyocyte Proliferation in Developmental Stage-Specific Manner with Pluripotent Stem Cells2013

    • Author(s)
      Uosaki H, Magadum A, Seo K, Fukushima H, Takeuchi A, Nakagawa Y, Moyes KW, Narazaki G, Kuwahara K, Laflamme M, Matsuoka S, Nakatsuji N, Nakao K, Kwon C, Kass DA, Engel FB, Yamashita JK
    • Journal Title

      Circ Cardiovasc Genet

      Volume: 6(6) Pages: 624-33

  • [Journal Article] Role of NRSF/REST in the Regulation of Cardiac Gene Expression and Function2013

    • Author(s)
      Kuwahara K
    • Journal Title

      Circ J

      Volume: 77(11) Pages: 2682-6

  • [Journal Article] Angiotensin II Type 1a receptor signaling directly contributes to the increased arrhythmogenicity in cardiac hypertrophy2013

    • Author(s)
      Yasuno S, Kuwahara K, Kinoshita H, Yamada C, Nakagawa Y, Usami S, Kuwabara Y, Ueshima K, Harada M, Nishikimi T, Nakao K
    • Journal Title

      Br J Pharmacol

      Volume: 170(7) Pages: 1384-95

  • [Journal Article] Adrenomedullin in Cardiovascular Disease : A Useful Biomarker, Its Pathological Roles and Therapeutic Application2013

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, Kangawa K, Nakao K
    • Journal Title

      Curr Protein Pept Sci

      Volume: 14(4) Pages: 256-267

  • [Journal Article] Increased Expression of HCN Channels in the Ventricular Myocardium Contributes to Enhanced Arrhythmicity in Mouse Failing Hearts2013

    • Author(s)
      Kuwabara Y, Kuwahara K, Takano M, Kinoshita H, Arai Y, Yasuno S, Nakagawa Y, Igata S, Usami S, Minami T, Yamada Y, Nakao K, Yamada C, Shibata J, Nishikimi T, Ueshima K, Nakao K
    • Journal Title

      J Am Heart Assoc

      Volume: 2(3) Pages: e000150

  • [Journal Article] Cardiac nuclear High Mobility Group Box 1 prevents the development of cardiac hypertrophy and heart failure2013

    • Author(s)
      Funayama A, Shishido T, Netsu S, Narumi T, Kadowaki S, Takahashi H, Miyamoto T, Watanabe T, Woo CH, Abe JI, Kuwahara K, Nakao K, Takeishi Y, Kubota I
    • Journal Title

      Cardiovasc Res

      Volume: 99(4) Pages: 657-64

  • [Journal Article] Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure2013

    • Author(s)
      Nishikimi T, Okamoto H, Nakamura M, Ogawa N, Horii K, Nagata K, Nakagawa Y, Kinoshita H, Yamada C, Nakao K, Minami T, Kuwabara Y, Kuwahara K, Masuda I, Kangawa K, Minamino N, Nakao K
    • Journal Title

      PLoS One

      Volume: 8(1) Pages: e53233

  • [Journal Article] Angiotensin II-induced cardiac hypertrophy and fibrosis are promoted in mice lacking Fgf162013

    • Author(s)
      Matsumoto E, Sasaki S, Kinoshita H, Kito T, Ohta H, Konishi M, Kuwahara K, Nakao K, Itoh N
    • Journal Title

      Genes Cells

      Volume: 18(7) Pages: 544-553

  • [Journal Article] Voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by angiotensin II in mice2013

    • Author(s)
      Nishida M, Ishikawa T, Saiki S, Sunggip C, Aritomi S, Harada E, Kuwahara K, Hirano K, Mori Y, Kim-Mitsuyama S
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 434(2) Pages: 210-6

  • [Journal Article] Determination of the B-type Natriuretic Peptide Level as a Criterion for Abnormalities in Japanese Individuals in Routine Clinical Practice : The J-ABS Multi-center Study (Japan Abnormal BNP Standard)2013

    • Author(s)
      Kawai M, Yoshimura M, Harada M, Mizuno Y, Hiramitsu S, Shimizu M, Shoda T, Kuwahara K, Miyagishima K, Ueshima K, Nakao K
    • Journal Title

      Intern Med

      Volume: 52(2) Pages: 171-7

  • [Journal Article] 109th Scientific Meeting of the Japanese Society of Internal Medicine : symposium : 2. Translational research and evidence-based medicine (EBM) in internal medicine in Japan, translational research; 4) Translational research of endocrinology and metabolism2012

    • Author(s)
      Hosoda K, Yasoda A, Ebihara K, Kuwahara K, Mukouyama M, Nakao K
    • Journal Title

      Nihon Naika Gakkai Zasshi

      Volume: 101(9) Pages: 2552-62

  • [Journal Article] Complexity of molecular forms of B-type natriuretic peptide in heart failure2012

    • Author(s)
      Nishikimi T, Kuwahara K, Nakagawa Y, Kangawa K, Minamino N, Nakao K
    • Journal Title

      Heart

      Volume: 99(10) Pages: 677-679

  • [Journal Article] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodeling in mice2012

    • Author(s)
      Minami T, Kuwahara K, Nakagawa Y, Takaoka M, Kinoshita H, Nakao K, Kuwabara Y, Yamada Y, Yamada C, Shibata J, Usami S, Yasuno S, Nishikimi T, Ueshima K, Sata M, Nakano H, Seno T, Kawahito Y, Sobue K, Kimura A, Nagai R and Nakao K
    • Journal Title

      EMBO J

      Volume: 31(23) Pages: 4428-40

  • [Journal Article] In vivo site-specific transfection of naked plasmid DNA in mice using a tissue suction device2012

    • Author(s)
      Shimizu K, Kawakami S, Hayashi K, Kinoshita H, Kuwahara K, Nakao K, Hashida M, Konishi S
    • Journal Title

      Plos One

      Volume: 7(7) Pages: e41319

  • [Journal Article] Transcriptional regulation of the fetal cardiac gene program2012

    • Author(s)
      Kuwahara K, Nishikimi T, Nakao K
    • Journal Title

      J Pharmacol Sci. 18

      Volume: 119(3) Pages: 198-203

  • [Journal Article] Fixed-dose combination therapy of candesartan cilexetil and amlodipine besilate for the treatment of hypertension in Japan2012

    • Author(s)
      Yasuno S, Fujimoto A, Nakagawa Y, Kuwahara K, Ueshima K
    • Journal Title

      Expert Rev Cardiovasc Ther

      Volume: 10(5) Pages: 577-83

  • [Journal Article] The effect of glycosylation on plasma N-terminal proBNP-76 levels in patients with heart or renal failure2012

    • Author(s)
      Nishikimi T, Ikeda M, Takeda Y, Ishimitsu T, Shibasaki I, Fukuda H, Kinoshita H, Nakagawa Y, Kuwahara K, Nakao K
    • Journal Title

      Heart

      Volume: 98(2) Pages: 152-61

  • [Journal Article] New Molecular Mechanisms for Cardiovascular Disease : Transcriptional Pathways and Novel Therapeutic Targets in Heart Failure2011

    • Author(s)
      Kuwahara K, Nakao K
    • Journal Title

      J Pharmacol Sci. 17

      Volume: 116(4) Pages: 337-342

  • [Journal Article] Induction and enhancement of cardiac cell differentiation from mouse and human induced pluripotent stem cells with cyclosporin-a2011

    • Author(s)
      Fujiwara M, Yan P, Otsuji TG, Narazaki G, Uosaki H, Fukushima H, Kuwahara K, Harada M, Matsuda H, Matsuoka S, Okita K, Takahashi K, Nakagawa M, Ikeda T, Sakata R, Mummery CL, Nakatsuji N, Yamanaka S, Nakao K, Yamashita JK
    • Journal Title

      PLoS One

      Volume: 6(2) Pages: e16734

  • [Journal Article] Current biochemistry, molecular biology, and clinical relevance of natriuretic peptides2011

    • Author(s)
      Nishikimi T, Kuwahara K, Nakao K
    • Journal Title

      J Cardiol

      Volume: 57(2) Pages: 131-140

  • [Journal Article] Zinc-finger protein 90 negatively regulates neuron-restrictive silencer factor-mediated transcriptional repression of fetal cardiac genes2011

    • Author(s)
      Hata L, Murakami M, Kuwahara K, Nakagawa Y, Kinoshita H, Usami S, Yasuno S, Fujiwara M, Kuwabara Y, Minami T, Yamada Y, Yamada Y, Nakao K, Ueshima K, Nishikimi T, and Nakao K
    • Journal Title

      J Mol Cell Cardiol

      Volume: 50(6) Pages: 972-981

  • [Presentation] TRPC3/6 as Potentially Novel Therapeutic Targets for the Treatment of Pulmonary Arterial Hypertension2014

    • Author(s)
      Kinoshita H, Kuwahara K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20140321-23
  • [Presentation] Elucidation of molecular mechanism of human proBNP : role of O-glycosylation in N-terminal region of proBNP2014

    • Author(s)
      Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Nakao K, Yamada C, Ueshima K, Minamino N, Kimura T, Nakao K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20140321-23
  • [Presentation] Molecular mechanism of lower processing rate in human proBNP : importance of the distance between the O-glycosylation and cleavage sites2014

    • Author(s)
      Nishikimi T, Nakagawa Y, Minamino N, Ikeda M, Ishimitsu T, Yamada C, Nakao K, Minami T, Kuwabara Y, Kinoshita H, Kangawa K, Kuwahara K, Nakao K
    • Organizer
      第78回日本循環器学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20140321-23
  • [Presentation] 維持血液透析患者におけるproBNPについての検討2013

    • Author(s)
      中川靖章, 錦見俊雄, 桑原宏一郎, 保野慎治, 木下秀之, 桒原佳宏, 中尾一泰, 山田千夏, 上嶋健治, 中尾一和
    • Organizer
      第17回日本心不全学会学術集会
    • Place of Presentation
      埼玉
    • Year and Date
      20131128-30
  • [Presentation] ナトリウム利尿ペプチド発現制御機構解明による心血管病治療標的の同定2013

    • Author(s)
      桑原宏一郎
    • Organizer
      第17回日本心血管内分泌代謝学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20131122-23
  • [Presentation] 維持血液透析患者における血中B型(脳性)ナトリウム利尿ペプチド前駆体についての検討2013

    • Author(s)
      中川靖章, 錦見俊雄, 桑原宏一郎, 保野慎治, 木下秀之, 桒原佳宏, 中尾一泰, 山田千夏, 上嶋健治, 中尾一和
    • Organizer
      第17回日本心血管内分泌代謝学会総会
    • Place of Presentation
      大阪
    • Year and Date
      20131122-23
  • [Presentation] O-glycosylated Pro B-type Natriuretic Peptide is Cleaved intracellularly By Furin in Ventricular Myocytes and Atrial Myocytes : Importance of the Distance Between the O-glycosylation Sites and Cleaved Sites2013

    • Author(s)
      Nishikimi T, Nakagawa Y, Minamino N, Ikeda M, Ishimitsu T, Yamada C, Nakao K, Minami T, Kuwabara Y, Kinoshita H, Kangawa K, Kuwahara K, Nakao K
    • Organizer
      AHA Scientific Sessoins 2013
    • Place of Presentation
      Dallas, USA
    • Year and Date
      20131116-20
  • [Presentation] 透析患者における血中B型(脳性)ナトリウム利尿ペプチド前駆体proBNPについての検討2013

    • Author(s)
      中川靖章, 錦見俊雄, 桑原宏一郎, 保野慎治, 木下秀之, 桒原佳宏, 中尾一泰, 山田千夏, 上嶋健治, 中尾一和
    • Organizer
      第61回心臓病学会
    • Place of Presentation
      熊本
    • Year and Date
      20130920-22
  • [Presentation] Blockade of TRPC6 is a Novel Therapeutic Approach Against Pathological Cardiac Remodeling2013

    • Author(s)
      Kinoshita H, Kuwahara K, Nishida M, Kurose H, Kiyonaka S, Mori Y, Yamada C, Kuwabara Y, Yasuno S, Nakagawa Y, Nishikimi T, Ueshima K, Nakao K
    • Organizer
      International Conference on Endothelin ET-13
    • Place of Presentation
      Tokyo
    • Year and Date
      20130908-11
  • [Presentation] Effect of hemodyalysis on precursor proBNP and glycosylated NT-proBNP in end-stage renal disease patients2013

    • Author(s)
      Nakagawa Y, Nishikimi T, Kuwahara K, Yasuno S, Kinoshita H, Kuwabara Y, Yamada C, Nakao K, Ueshima K, Nakao K
    • Organizer
      European Society of Cardiology 2013 (ESC 2013)
    • Place of Presentation
      Amsterdam, Netherland
    • Year and Date
      20130831-0904
  • [Presentation] Myocardin-related transcription factor-A plays a pivotal role in vascular remodeling2013

    • Author(s)
      Kuwahara K, Nakao K
    • Organizer
      第45回日本動脈硬化学会
    • Place of Presentation
      東京
    • Year and Date
      20130718-19
  • [Presentation] 肺動脈性肺高血圧症に対する新規治療標的としてのTRPC3/6阻害効果の検討2013

    • Author(s)
      木下秀之, 桑原宏一郎, 清中茂樹, 森泰生, 赤木達, 中村一文, 桒原佳宏, 中川靖章, 錦見俊雄, 中尾一和
    • Organizer
      第2回日本肺循環学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20130622-23
  • [Presentation] 透析患者における血中N端proBNPの糖鎖修飾と測定系への影響について2013

    • Author(s)
      中川靖章, 錦見俊雄, 桑原宏一郎, 保野慎治, 木下秀之, 桒原佳宏, 中尾一泰, 山田千夏, 上嶋健治, 中尾一和
    • Organizer
      第2回臨床高血圧フォーラム
    • Place of Presentation
      東京
    • Year and Date
      20130525-26
  • [Presentation] Glycosylation of plasma N-terminal proBNP and its effect on NT-proBNP assay in hemodyalysis patients2013

    • Author(s)
      Yasuaki Nakagawa, Toshio Nishikimi, , Koichiro Kuwahara Yoshihiro Kuwabara, , Hideyuki Kinoshita, Makoto Takano, Satoru Usami, Kazuhiro Nakao, Takeya Minami, Yuko Yamada, Chinatsu Yamada, Junko Shibata, Kenji Ueshima and Kazuwa Nakao
    • Organizer
      第77回日本循環器学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      20130315-17
  • [Presentation] Molecular mechanisms underlying cardioprotective effects of natriuretic peptide2012

    • Author(s)
      Koichiro Kuwahara, Kazuwa Nakao
    • Organizer
      The 7th Oulu Symposium
    • Place of Presentation
      Oulu, Finland
    • Year and Date
      20120830-0902
  • [Presentation] Translational Research of Natriuretic Peptide in Cardiovascular Disease2012

    • Author(s)
      Koichiro Kuwahara, Kazuwa Nakao (Meet the Experts)
    • Organizer
      The76th Annual Scientific Meeting of The Japanese CirculationSociety
    • Place of Presentation
      Fukuoka International Congress Center, Fukuoka, Japan
    • Year and Date
      20120316-18
  • [Presentation] TRPC3/6 Ion Channels as Potentially Novel Therapeutic Targets against Pulmonary Arterial Hypertension2012

    • Author(s)
      Hideyuki Kinoshita, Koichiro Kuwahara, Shigeki Kiyonaka, Yasuo Mori, Junko Shibata, Chinatu Yamada, Takeya Minami, Kazuhiro Nakao, Yoshihiro Kuwabara, Shinji Yasuno, Satoru Usami, Yasuaki Nakagawa, Toshio Nishikimi, Kenji Ueshima, KazuwaNakao
    • Organizer
      The76th Annual Scientific Meeting of The Japanese CirculationSociety
    • Place of Presentation
      Fukuoka International Congress Center, Fukuoka, Japan
    • Year and Date
      20120316-18
  • [Presentation] BNP遺伝子発現調節領域におけるserum response factor応答領域の新たなる同定とその心筋細胞肥大反応における意義2011

    • Author(s)
      桑原宏一郎・ 木下秀之・ 桒原佳宏・ 中川靖章・ 南 丈也・ 山田千夏・ 柴田純子・宇佐美覚・ 錦見俊雄・ 中尾一和
    • Organizer
      第15回日本心血管内分泌学会
    • Place of Presentation
      大阪
    • Year and Date
      20111125-26
  • [Presentation] Blockade of TRPC6/3 is a Novel Therapeutic Approach for Preventing Pathological Cardiac Hypertrophy2011

    • Author(s)
      Hideyuki Kinoshita, Koichiro Kuwahara, Motohiro Nishida, Hitoshi Kurose, Shigeki Kiyonaka, Yasuo Mori, Yoshihiro Kuwabara, Yasuaki Nakagawa, Kenji Ueshima, Kazuwa Nakao
    • Organizer
      European Society of Cardiology Congress
    • Place of Presentation
      Paris, France
    • Year and Date
      20110827-31
  • [Book] ガイドライン外来診療20142014

    • Author(s)
      桑原宏一郎, 木村剛
    • Total Pages
      455-460
    • Publisher
      日経メディカル開発
  • [Book] 変貌する心不全診療2013

    • Author(s)
      中川靖章, 桑原宏一郎
    • Publisher
      南江堂
  • [Book] 最新内分泌代謝学2013

    • Author(s)
      桑原宏一郎
    • Total Pages
      274- 277
    • Publisher
      診断と治療社
  • [Book] 心不全診療Q&Aエキスパート106人からの回答2012

    • Author(s)
      桑原宏一郎
    • Total Pages
      205-20
    • Publisher
      中外医学社
  • [Remarks]

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~med2/jpn/research/cardio.html

URL: 

Published: 2015-06-25  

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