Novel pharmacotherapy for ischemic heart disease with cardioprotective activity of endogenous acetylcholine.

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790729
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kochi University
• Principal Investigator: ARIKAWA Mikihiko Kochi University, 教育研究部医療学系, 助教 (20432817)
• Project Period (FY): 2009 – 2010
• Keywords: 生体機能利用 / 心機能保護 / コリンエステラーゼ阻害剤 / アセチルコリン

Research Abstract

In the present study, we investigated the acute effect of donepezil, an acetylcholinesterase inhibitor, on cardiac dysfunction and remodeling during an acute phase of myocardial infarction (MI) in mice. As results, donepezil inhibited matrix metalloproteinase-9 (MMP-9)-related acute inflammatory tissue injury in the infarcted myocardium, thereby reduced the risk of left ventricular free wall rupture during the acute phase of MI.

Research Products

• [Journal Article] Donepezil, anti-Alzheimer's Disease Drug, Prevents Cardiac Rupture during Acute Phase of Myocardial Infarction in Mice. (2011)
  • Author(s): Arikawa M, Kakinuma Y, Handa T, Yamasaki F, Sato T.
  • Journal Title: PLoS ONE in press
  • Peer Reviewed
• [Journal Article] Differential regulation of TNF receptors by vagal nerve stimulation protect heart against acute ischemic injury. (2010)
  • Author(s): Katare RG, Ando M, Kakinuma Y, Arikawa M, Yamasaki F, Sato T.
  • Journal Title: J Mol Cell Cardiol 49 Pages: 234-244
  • Peer Reviewed
• [Journal Article] Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model. (2010)
  • Author(s): Kakinuma Y, Furihata M, Akiyama T, Arikawa M, Handa T, Katare RG, Sato T.
  • Journal Title: J Mol Cell Cardiol 48 Pages: 680-693
  • Peer Reviewed
• [Journal Article] Anti-Alzheimer's drug, donepezil, markedly improves long-term survival after chronic heart failure in mice. (2009)
  • Author(s): Handa T, Katare RG, Kakinuma Y, Arikawa M, Ando M, Sasaguri S, Yamasaki F, Sato T.
  • Journal Title: J Card Fail 15 Pages: 805-811
  • Peer Reviewed
• [Journal Article] Donepezilを使用した容量負荷心不全マウスにおける心機能改善効果、生存率改善効果の検討 (2009)
  • Author(s): 半田武巳、Katare GR、柿沼由彦、有川幹彦、安藤元紀、山崎文靖、佐藤隆幸、篠栗志朗
  • Journal Title: 心臓 41 Pages: 115-123
  • Peer Reviewed
• [Journal Article] Chronic intermittent fasting improves the survival following large myocardial ischemia by activation of BDNF/VEGF/PI3K signaling pathway. (2009)
  • Author(s): Katare GR, Kakinuma Y, Arikawa M, Yamasaki F, Sato T.
  • Journal Title: J Mol Cell Cardiol 46 Pages: 405-412
  • Peer Reviewed
• [Journal Article] Vagal nerve stimulation prevents reperfusion injury through inhibition of opening of mitochondrial permeability transition pore independent of the bradycardiac effect. (2009)
  • Author(s): Katare GR, Ando M, Kakinuma Y, Arikawa M, Handa T, Yamasaki F, Sato T.
  • Journal Title: J Thorac Cardiovasc Surg 137 Pages: 223-231
  • Peer Reviewed
• [Presentation] Donepezil, an acetylcholinesterase inhibitor, reduces the risk of left ventricular free wall rupture during an acute phase of myocardial infarction by attenuating macrophage matrix metalloproteinase-9. (2010)
  • Author(s): Arikawa M, Kakinuma Y, Zheng C, Yamasaki F, Sato T.
  • Organizer: 19th International Conference of the Cardiovascular System Dynamics Society
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20100923-20100926
• [Presentation] Effects of a non-neuronal cholinergic system equipped for cardiomyocytes, as a molecular brake, on overshooting cardiac energy metabolism. (2010)
  • Author(s): Kakinuma Y, Akiyama T, Arikawa M, Sato T.
  • Organizer: 19th International Conference of the Cardiovascular System Dynamics Society
  • Place of Presentation: Fukuoka, Japan
  • Year and Date: 20100923-20100926
• [Presentation] Effects of a non-central and non-neuronal acetylcholine synthesis system equipped for cardiomyocytes, as a molecular brake, on overshooting cardiac energy metabolism. (2010)
  • Author(s): 柿沼由彦、秋山剛、有川幹彦、半田武巳、佐藤隆幸
  • Organizer: 第31回日本循環制御医学会総会
  • Place of Presentation: 大阪府豊中市
  • Year and Date: 20100528-20100529
• [Presentation] Effects of a non-neuronal acetylcholine synthesis system equipped for cardiomyocytes, as a molecular brake, on overshooting cardiac energy metabolism. (2010)
  • Author(s): Kakinuma Y, Akiyama T, Arikawa M, Handa T, Sato T.
  • Organizer: 第74回日本循環器学会総会・学術集会
  • Place of Presentation: 京都市
  • Year and Date: 20100305-20100307
• [Presentation] Donepezil, An acetylcholinesterase inhibitor against Alzheimer's dementia, prevents remodeling and improves survival in volume overload heart failure mice. (2009)
  • Author(s): Handa T, Katare RG, Kakinuma Y, Arikawa M, Sasaguri S, Yamasaki F, Sato T.
  • Organizer: American College of Cardiology 58th Annual Scientific Session
  • Place of Presentation: Orlando USA
  • Year and Date: 20090328-20090331
• [Presentation] Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, prevents remodeling in volume-overload heart failure mice: Local and central effect of donepezil (2009)
  • Author(s): Handa T, Kakinuma Y, Arikawa M, Sasaguri S, Yamasaki F, Sato T.
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪市
  • Year and Date: 20090320-20090321