New target of chronic heart failure treatment by cholinesterase inhibitor (donepezil)

• Project/Area Number: 20790534
• 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: HANDA Takemi Kochi University, 医学部附属病院, 医員 (00437716)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 分子心臓病態学 / 循環器・心不全 / 心筋梗塞 / リモデリング抑制 / ANPmRNA活性化 / アセチルコリン

Research Abstract

We reported that the mechanism of cholinesterase inhibitor (donepezil) for chronic heart failure (CHF) treatment. 1. Donepezil activated PI3K/Akt/HIF/VEGF cell survival pathway. 2. Donepezil induced HIF under CHF condition, and HIF activated myocardial ANPmRNA expression which induced natriuretic effects.
This study suggested that ANPmRNA expression induced by donepezil protected myocardium under hypoxic condition.

Research Products

• [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: Mol Cell Cardiol (印刷中)
  • NAID: 120002069739
  • Peer Reviewed
• [Journal Article] Donepezil, an acetylcholinesterase inhibitor against Alzheimer's dementia, promotes angiogenesis in an ischemic hindlimb model. (2010)
  • Author(s): Kakinuma, Y
  • Journal Title: J Mol Cell Cardiol. (in press)
  • 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: Card Fail 15巻 Pages: 805-811
  • 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 RG, Ando M, Kakinuma Y, Arikawa M, Handa T, Yamasaki F, Sato T
  • Journal Title: J Thorac Cardiovasc Surg 137巻 Pages: 223-231
  • Peer Reviewed
• [Journal Article] Donepezilを利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, カタレ, ラジェシュG, 柿沼由彦, 有川幹彦, 安藤元紀, 山崎文靖, 佐藤隆幸, 笹栗志朗
  • Journal Title: 心臓 41巻 Pages: 115-123
  • 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
  • Journal Title: Journal of Cardiac Failure 15 Pages: 805-811
  • Peer Reviewed
• [Journal Article] Donepezilを利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
  • Journal Title: 心臓 41 Pages: 115-123
  • 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, RG
  • Journal Title: J Thorac Cardiovasc Surg 137 Pages: 223-231
  • Peer Reviewed
• [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.
  • Organizer: 第74回日本循環器病学会総会・学術集会
  • Place of Presentation: 京都府国立京都国際会館
  • Year and Date: 2010-03-06
• [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.
  • Organizer: American college of cardiology 58th Annual Scientific Session
  • Place of Presentation: Orland, USA
  • Year and Date: 2009-03-29
• [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): 半田武巳
  • Organizer: 第73回日本循環器病学会総会・学術集会
  • Place of Presentation: 大阪市大阪国際会議場
  • Year and Date: 2009-03-21
• [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): 半田武巳
  • Organizer: 第73回日本循環器病学会総会・学術集会
  • Place of Presentation: 大阪市, 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] Donepezil, an Acetylcholinesterase Inhibitor Against Alzheimer's Dementia, Prevents Remodeling and Improves Survival in Volume-Overload Heart Failure MiceAmerican college of cardiology 58th Annual Scientific Session (2009)
  • Author(s): 半田武巳
  • Organizer: American college of cardiology 58th Annual Scientific Session
  • Place of Presentation: Orland, USA
  • Year and Date: 2009-03-21
• [Presentation] Cardiomyocytes produces acethylcholine in response to muscarinic receptor stimulation: A possible mechanism for amplification of cardioprotective effects of cardiac vagal nerve (2008)
  • Author(s): Kakinuma Y.
  • Organizer: American Heart Association Scientific sessions 2008
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-12
• [Presentation] Cardiomyocytes produces acethylcholine in response to muscarinic receptor stimulation : A possible mechanism for amplification of cardioprotective effects of cardiac vagal nerve (2008)
  • Author(s): Kakinuma Y
  • Organizer: American Heart Association Scientific sessions 2008
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-12