The treatment benefit of ghrelin on a mouse model of inherited dilated cardiomyopathy caused by troponin mutation

• Project/Area Number: 25871236
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine; General pharmacology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: ZHAN DONGYUN 独立行政法人国立循環器病研究センター, 研究所, 流動研究員 (30616941)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 拡張型心筋症 / ノックインマウス / 生理活性ペプチド / 心臓自律神経活動 / 心拍変動 / 分子心臓学 / 生理活性物質

Outline of Final Research Achievements

We examined whether ghrelin is beneficial for the treatment of inherited dilated cardiomyopathy (DCM) with a deletion mutation ΔK210 in the cardiac troponin T gene using a knock-in mouse model.We found that ghrelin administration for one month suppressed the excessive cardiac sympathetic nerve activity and recovered the cardiac parasympathetic nerve activity and then prevented sudden death and left ventricular remodeling of DCM mice. These results suggested that cardiovascular benefits of ghrelin are likely linked to the suppression of CSNA and recovery of cardiac parasympathetic nerve activity.

Research Products

• [Journal Article] In vivo effects of propyl gallate, a novel Ca(2+) sensitizer, in a mouse model of dilated cardiomyopathy caused by cardiac troponin T mutation. (2014)
  • Author(s): Cheng-Kun Du, Dong-Yun Zhan, Sachio Morimoto
  • Journal Title: Life Sciences Volume: 109 Issue: 1 Pages: 15-19
  • DOI: 10.1016/j.lfs.2014.06.004
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy (2014)
  • Author(s): Cheng-Kun Du, Dong-Yun Zhan, Sachio Morimoto, Tsuyoshi Akiyama, Daryl O. Schwenke, Hiroshi Hosoda, Kenji Kangawa, Mikiyasu Shirai
  • Journal Title: Pharmacology Research & Perspectives Volume: ２ Issue: 5
  • DOI: 10.1002/prp2.64
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Myocardial interstitial levels of serotonin and its major metabolite, 5-hydroxyindole acetic acid, in in vivo rat heart (2014)
  • Author(s): Cheng-Kun Du, Dong-Yun Zhan, Tsuyoshi Akiyama, Takashi Sonobe, Tadakatsu Inagaki, Mikiyasu Shirai
  • Journal Title: Life Sciences Volume: １１７ Issue: 1 Pages: 33-39
  • DOI: 10.1016/j.lfs.2014.09.019
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Contribution of calpain to myoglobin efflux from cardiomyocytes during ischaemia and after reperfusion in anaesthetized rats (2014)
  • Author(s): Takashi Sonobe, Akiyama Tsuyoshi, Cheng-Kun Du, Dong-Yun Zhan, Mikiyasu Shirai
  • Journal Title: Acta Physiologica Volume: 210(4) Pages: 823-831
  • Peer Reviewed
• [Journal Article] In vivo monitoring of acetylcholine release from cardiac vagal nerve endings in anesthetized mice (2013)
  • Author(s): Dong-Yun Zhan, Cheng-Kun Du, Akiyama Tsuyoshi, Takashi Sonobe, Hirotsugu Tsuchimochi, Shuji Shimizu, Toru Kawada, Mikiyasu Shirai
  • Journal Title: Autonomic Neuroscience: Basic and Clinical Volume: 176(1-2) Pages: 91-94
  • Peer Reviewed
• [Journal Article] Contribution of serotonin uptake and degradation to myocardial interstitial serotonin levels during ischaemiareperfusion in rabbits (2013)
  • Author(s): Takashi Sonobe, Akiyama Tsuyoshi, Cheng-Kun Du, Dong-Yun Zhan, Mikiyasu Shirai
  • Journal Title: Acta Physiologica Volume: 207 Pages: 260-268
  • Peer Reviewed
• [Presentation] Survival benefit of ghrelin in the heart failure due to dilated cardiomyopathy. (2015)
  • Author(s): Zhan Dongyun, Du Chengkun, Morimoto Sachio, Akiyama Tsuyoshi , Schwenke Daryl, Hosoda Hiroshi, Kangawa Kenji, Shirai Mikiyasu.
  • Organizer: The 92th annual meeting of the physiological society of Japan
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Knock-in mouse model of hypertrophic cardiomyopathy caused by troponin T mutation. (2015)
  • Author(s): Du Chengkun, Zhan Dongyun, Morimoto Sachio, Shirai Mikiyasu.
  • Organizer: The 92th annual meeting of the physiological society of Japan
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Role of monoamine oxidase on hydroxyl radical production during ischemia/reperfusion in anesthetized rats. (2015)
  • Author(s): Inagaki Tadakatsu, Akiyama Tsuyoshi, Zhan Dongyun, Du Chengkun, Shirai Mikiyasu.
  • Organizer: The 92th annual meeting of the physiological society of Japan
  • Place of Presentation: 神戸国際会議場・展示場
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] 中枢を介した迷走神経活性化による拡張型心筋症治療薬 (2015)
  • Author(s): 戦 冬雲、杜 成坤、秋山 剛、白井 幹康
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 心筋トロポニンT突然変異による肥大型心筋症ノックインマウスモデル (2015)
  • Author(s): 杜 成坤、 戦 冬雲、森本 幸生、白井 幹康
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] The treatment benefit of ghrelin on a mouse model of inherited dilated cardiomyopathy caused by troponin mutation. (2015)
  • Author(s): Dong-Yun Zhan, Cheng-Kun Du, Sachio Morimoto, Tsuyoshi Akiyama, Daryl O. Schwenke, Hiroshi Hosoda, Kenji Kangawa Mikiyasu Shirai.
  • Organizer: Biophysical society 59th annual meeting
  • Place of Presentation: Baltimore, Maryland, USA
  • Year and Date: 2015-02-07 – 2015-02-11
• [Presentation] Myocardial interstitial serotonin and its major metabolite, 5-hydroxyindole acetic acid levels determined by microdialysis technique in in vivo rat heart. (2015)
  • Author(s): Cheng-Kun Du, Dong-Yun Zhan, Tsuyoshi Akiyama, Takashi Sonobe, Tadakatsu Inagaki, Mikiyasu Shirai.
  • Organizer: Biophysical society 59th annual meeting
  • Place of Presentation: Baltimore, Maryland, USA
  • Year and Date: 2015-02-07 – 2015-02-11
• [Presentation] DCMノックインマウスにおける心臓迷走神経調節機構 (2014)
  • Author(s): 戦 冬雲、杜 成坤、秋山 剛、森本 幸生、清水 秀二、川田 徹、白井 幹康
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] 虚血/再灌流における心筋間質セロトニンの動態 (2014)
  • Author(s): 杜 成坤、戦 冬雲、秋山 剛、稲垣 薫克、白井 幹康
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] 4-HBを用いた心筋虚血再灌流のヒドロキシラジカル測定 (2014)
  • Author(s): 稲垣 薫克、秋山 剛、、戦 冬雲、杜 成坤、白井 幹康
  • Organizer: 第91回日本生理学会大会
  • Place of Presentation: 鹿児島
• [Presentation] DCMノックインマウスにおける心臓迷走神経調節機構 (2014)
  • Author(s): 戦 冬雲、杜 成坤、秋山 剛、森本 幸生、清水 秀二、川田 徹、白井 幹康
  • Organizer: 第87回日本薬理学会大会
  • Place of Presentation: 仙台
• [Presentation] 虚血/再灌流における心筋間質セロトニンの動態 (2014)
  • Author(s): 杜 成坤、戦 冬雲、秋山 剛、稲垣 薫克、白井 幹康
  • Organizer: 第87回日本薬理学会大会
  • Place of Presentation: 仙台
• [Presentation] 拡張型心筋症ノックインマウスに対するグレリンの治療効果 (2013)
  • Author(s): 杜 成坤、戦 冬雲、森本 幸生、秋山 剛、寒川 賢治、白井 幹康
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
• [Presentation] うっ血性心不全の病態生理学における脳セロトニン機能障害の役割 (2013)
  • Author(s): 李 蕾、森本 幸生、武 幸子、戦 冬雲、杜 成坤、王 媛媛、範 雪麗、吉原 達也、高橋 富美、片渕 俊彦、笹栗 俊之
  • Organizer: 第17回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪