Molecular mechanisms of left ventricular diastolic dysfunction in the type 2 diabetic heart

• Project/Area Number: 25860611
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Cardiovascular medicine
• Research Institution: Sapporo Medical University
• Principal Investigator: KOUZU Hidemichi 札幌医科大学, 医学部, 助教 (60596609)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 拡張機能 / 糖尿病 / 心不全 / AMP deaminase / 拡張機能障害 / エネルギー代謝

Outline of Final Research Achievements

The aim of this study was to examine mechanisms by which type 2 diabetes (T2DM) augments ventricular diastolic stiffness in response to pressure overloading. We found that AMP deaminse activity was increased in T2DM hearts, resulting in excessive degradation of adenine nucleotides and ATP depletion during pressure overloading. ATP level was negatively correlated with tau of LV pressure and LVEDP. These diastolic properties were observed before development of extracellular matrix or titin remodeling.

Research Products

• [Journal Article] Excessive degradation of adenine nucleotides by up-regulated AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart (2015)
  • Author(s): Hidemichi Kouzu, Takayuki Miki, Masaya Tanno, Atsushi Kuno, Toshiyuki Yano, Takahito Itoh, Tatsuya Sato, Daisuke Sunaga, Hiromichi Murase, Toshiyuki Tobisawa, Makoto Ogasawara, Satoko Ishikawa, Tetsuji Miura
  • Journal Title: J Mol Cell Cardiol Volume: 80 Pages: 136-145
  • DOI: 10.1016/j.yjmcc.2015.01.004
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Insufficient ATP supply due to excessive degradation of adenine nucleotides by AMP deaminase underlies afterload-induced diastolic dysfunction in the type 2 diabetic heart (2014)
  • Author(s): Hidemichi Kouzu, Takayuki Miki, Masaya Tanno, Atsushi Kuno, Toshiyuki Yano, Hiromichi Murase, Toshiyuki Tobisawa, Makoto Ogasawara, Shingo Muratsubaki, Tetsuji Miura
  • Organizer: The 36th Congress of the European Society of Cardiology
  • Place of Presentation: Barcelona
  • Year and Date: 2014-08-30 – 2014-09-03
• [Presentation] Insufficient ATP supply due to excessive degradation of adenine nucleotides underlies after load-induced diastolic dysfunction in type 2 diabetic heart (2013)
  • Author(s): Hidemichi Kouzu, Takayuki Miki, Masaya Tanno, Atsushi Kuno, Toshiyuki Yano, Hiromichi Murase, Toshiyuki Tobisawa, Makoto Ogasawara, Tetsuji Miura
  • Organizer: The 17th Annual Scientific Meeting of the Japanese Heart Failure Society
  • Place of Presentation: さいたま市