Heart failure rescued by an anti-viral drug which inhibits cardiacadenylyl cyclasefor aging society

• Project/Area Number: 22590811
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Yokohama City University
• Principal Investigator: TSUNEMATSU Takashi 横浜市立大学, 医学研究科, 客員准教授 (70347300)
• Co-Investigator(Kenkyū-buntansha): OKUMURA Satoshi 鶴見大学, 歯学部, 教授 (60233475) ; KUROTANI Reiko 山形大学, 大学院・理工学研究科, 助教 (00453043) ; IWATSUBO Kosaku 横浜市立大学, 医学研究科, 客員准教授 (90363796)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: シグナル伝達 / 循環器・高血圧 / サイクリックAMP / 心不全 / 循環器高血圧

Research Abstract

The aim of this study is to developa cardiac adenylyl cyclase inhibitor as a drug for the treatment of heart failure and arrhythmia. We have demonstrated that a pharmacological inhibitor of AC5,Vidarabine,and a newly developed and water-soluble vidarabine prodrugameliorates the development of heart failure and arrhythmia(H22-23). We also confirmed the effectiveness ofvidarabine on atrial fibrillation aftercardiac surgery in humans in Yokohama City University Hospital with thecollaboration of cardiac surgerygroup(H24).

Research Products

• [Journal Article] Pharmacological stimulation of type 5 adenylyl cyclase stabilizes heart rate under both microgravity and hypergravity induced by parabolic flight (2012)
  • Author(s): Bai Y,Tsunematsu T, Jiao Q, Ohnuki Y, Mototani Y, Shiozawa K, Jin M, Cai W, Jin HL, Fujita T, Ichikawa Y, Suita K, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 119 Pages: 381-189
  • NAID: 10031071685
  • Peer Reviewed
• [Journal Article] Prevention of heart failure in mice by an antiviral agent that inhibits type 5 cardiac adenylyl cyclase (2012)
  • Author(s): Iwatsubo K, Bravo C, Uechi M, Baljinnyam E, Nakamura T, Umemura S, Lai L, Gao S, Yan L, Zhao X, Park M, Qiu H, Okumura S, Iwatsubo M, Vatner SF, Vatner DE
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 302
  • Peer Reviewed
• [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate Under Both Microgravity and Hypergravity Induced by Parabolic Flight (2012)
  • Author(s): Bai Y, et al.
  • Journal Title: Journal of Pharmacological Sciences Volume: 119 Issue: 4 Pages: 381-389
  • DOI: 10.1254/jphs.12102FP
  • NAID: 10031071685
  • ISSN: 1347-8613, 1347-8648
  • Peer Reviewed
• [Presentation] Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against stress (2012)
  • Author(s): Satoshi Okumura, Meihua Jing, Yoshiki Ohnuki, Iyuki Namekata, Reiko Kurotani, Takayuki Fujita, Hui-Ling Jin, Wengian Cai, Yunzhe Bai, Kenji Suita, Takashi Tsunematsuet al
  • Organizer: American Heart Association Scientific Scission
  • Place of Presentation: Los Angeles, California, USA
  • Year and Date: 2012-11-06
• [Presentation] Disruption of Epac1 decreases phosphorylation of phospholamban and protects the heart against stress (2012)
  • Author(s): Satoshi Okumura, Meihua Jing, Yoshiki Ohnuki, Iyuki Namekata, Reiko Kurotani, Takayuki Fujita, Hui-Ling Jin, Wengian Cai, Yunzhe Bai, Kenji Suita, Takashi Tsunematsu et al.
  • Organizer: American Heart Association Scientific Scission 2012
  • Place of Presentation: Los Angeles, USA
• [Presentation] Epac activation protects heart from interleukin-6-induced cardiac dysfunction by inhibiting STAT/iNOS signaling (2011)
  • Author(s): Satoshi Okumura, Meihua Jin, Fumika Kawamata, Hui-Ling Jin, Wenqian Cai, Yunzhe Bai, Kenji Suita, Yuko Hidaka, Takashi Tsunematsu, Yoshihiro Ishikawa
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlando in USA
  • Year and Date: 2011-11-15
• [Presentation] Epac activation protects heart from interleukin-6-induced cardiac dysfunction by inhibiting STAT/iNOS signaling (2011)
  • Author(s): Satoshi Okumura, Meihua Jin,Fumika Kawamata, Hui-LingJin, Wenqian Cai, Yunzhe Bai, Kenji Suita, Yuko Hidaka, Takashi Tsunematsu, Yoshihiro Ishikawa
  • Organizer: American Heart Association Scientific Sessions 2011
  • Place of Presentation: Orlandoin USA
  • Year and Date: 2011-11-14
• [Presentation] Disruption of Epac1 Protects Heart from Catecholamine-mediated Cardiac Fibrosis. (2011)
  • Author(s): OkumuraS,CaiW,JinM, Bai Y, TsunematsuT, HidakaY, KurotaniR, IshikawaY
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 横浜パシフィコ(神奈川県)
  • Year and Date: 2011-08-03
• [Presentation] Disruption of Epac 1 protects heart from catecholamine-mediated cardiac fibrosis (2011)
  • Author(s): Satoshi Okumura S, Wenqian Cai, Meihua Jin, Yunzhe Bai, Takashi Tsunematsu, Yuko Hidaka, Reiko Kurotani, Yoshihiro Ishikawa
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: パシフィコ横浜(横浜市)
  • Year and Date: 2011-08-03
• [Presentation] Disruption of Epac1 Protects Heart from Catecholamine-mediated Cardiac Fibrosis (2011)
  • Author(s): Satoshi Okumura, Wenqian Cai, Meihua Jin, Bai Yunzhe, Takashi Tsunematsu, Yuko Hidaka, Reiko Kurotani, Yoshihiro Ishikawa
  • Organizer: The 75^<th> Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama in Japana(抄録採択:震災のため中止)
• [Remarks] 横浜市立大学循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/
• [Remarks] 横浜市立大学大学院医学研究科 循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/
• [Remarks] 横浜市立大学循環制御医学ホームページ
• [Remarks] 横浜市立大学循環制御医学ホームページ
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2012)
  • Inventor(s): 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Holder: 横浜市立大学
  • Filing Date: 2012-08-01
  • Overseas
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2012)
  • Inventor(s): 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Holder: 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-08-01
• [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤 (2011)
  • Inventor(s): 石川義弘、奥村敏、星野雄二郎、井上誠一
  • Industrial Property Rights Holder: 横浜市立大学、横浜国立大学
  • Filing Date: 2011-10-20
• [Patent(Industrial Property Rights)] ビダラビンによる心房細動治療 (2011)
  • Inventor(s): 石川義弘、奥村敏、吹田憲治
  • Industrial Property Rights Holder: 横浜市立大学
  • Industrial Property Number: 2011-222421
  • Filing Date: 2011-10-07
  • Overseas
• [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤 (2010)
  • Inventor(s): 石川義弘、奥村敏、星野雄二郎、井上誠一
  • Industrial Property Rights Holder: 横浜市立大学、横浜国立大学
  • Industrial Property Number: 2010-240301
  • Filing Date: 2010-10-27