The New Therapeutic Approach to Left Ventricular Remodeling Progression via Cardiac Autophagy

2013 Fiscal Year Final Research Report

• Project/Area Number: 24790751
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Circulatory organs internal medicine
• Research Institution: Gifu University
• Principal Investigator: KANAMORI Hiromitsu 岐阜大学, 医学部附属病院, 助教 (20456502)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: オートファジー / リモデリング / 心筋梗塞 / 心不全 / レスベラトロール / 心保護

Research Abstract

Autophagy compensate the lack of energy in cardiomyocyte suffering from acute or old myocardial infarction. However there is no clinical therapeutic approach via cardiac autophagy yet. Then we investigated the effect of resveratrol, a popular natural polyhenolic compound with antioxidant and proautophagic actions, on postinfarction heart failure using mouse myocardial infarction model. Resveratrol reversed left ventricular dilatation (reverse remodeling) and significantly improved cardiac dysfunction. Autophagy was augmented in those heart as shown autophagy related protein expression and ultrastructure findings including autophagic vacuoles. Resveratrol enhanced the activity of AMPK and suppressed the activity of mTOR and p70S6 kinese. Myocardial ATP production was increased in those heart. In conclusion, resveratrol is a beneficial pharmacological tool that augments autophagy to bring about reverse remodeling in the post infarction heart.

Research Products

• [Journal Article] Resveratrol reverses remodeling in hearts with large, old myocardial infarctions through enhanced autophagy-activating AMP Kinase pathway (2013)
  • Author(s): Kanamori H, Takemura G, Goto K, Tsujimoto A, Ogino A, Takeyama T, Kawaguchi T, Watanabe T, Morishita K, Kawasaki M, Mikami A, Fujiwara T, Fujiwara H, Seishima M,Minatoguchi S
  • Journal Title: Am J Pathol Volume: 182(3) Pages: 701-13
  • Peer Reviewed
• [Presentation] Resveratrol Promotes Postinfarction Left Ventricular Reverse Remodeling via Autophagy activating AMP Kinase Pathway independent of Sirt 1 (2012)
  • Organizer: 第16回 日本心不全学会・学術集会
  • Place of Presentation: 仙台
  • Year and Date: 20121130-1202
• [Presentation] Resveratrol Displays Cardioprotection in Postinfarction Remodeling Through Autophagic Activation Associated with AMPK but not Sirt1 Pathway (2012)
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Los Angeles USA
  • Year and Date: 20121103-07
• [Presentation] Resveratrol Promotes Reverse Remodeling and Mitigates Heart Failure of Post-Myocardial Infarction via Autophagy Activating AMP Kinase Pathway (2012)
  • Organizer: 第76回日本循環器学会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120316-18
• [Presentation] Resveratrol Brings About Reverse Remodeling in the Heart with a Large Old Myocardial Infarction Through Autophagy Activating AMP Kinase Pathway (2011)
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: orlando USA
  • Year and Date: 20111113-16
• [Presentation] Resveratrol Mitigates Postinfarction Left Ventricular Adverse Remodeling and Cardiac Dysfunction via Autophagy Activating AMP Kinase Pathway (2011)
  • Organizer: 第15回日本心不全学会・学術集会
  • Place of Presentation: 鹿児島
  • Year and Date: 20111013-15