Temporal spatial analysis and physiological significance of ATP variability in myocardial infarction by ATP-visualized mice

• Project/Area Number: 16K09491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Gunma University
• Principal Investigator: Koitabashi Norimichi 群馬大学, 医学部附属病院, 助教 (10420093)
• Co-Investigator(Kenkyū-buntansha): 倉林 正彦 群馬大学, 大学院医学系研究科, 教授 (00215047)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 心臓 / エネルギー代謝 / 可視化 / 虚血 / 遺伝子改変動物 / 生体イメージング / 可視化技術 / 循環器・高血圧 / 生体分子 / 生理学 / 応用動物

Outline of Final Research Achievements

We succeeded for the first time in the world to create genetically modified mice expressing FRET protein GO-ATeam that can visualize changes in ATP concentrations in real time. In addition, the applicant was able to visualize and quantify changes in the ATP concentration of the heart beating in real time in vivo. It was found that the ATP concentration of the heart fluctuates with the change of the oxygen consumption when the amount of ATP of the heart was examined over time by an acute load by using this mouse. Acute ischemia found that ATP is transiently increased in ischemic area. It was found that the ATP level of the heart was hardly changed even in heart failure and diabetes.

Academic Significance and Societal Importance of the Research Achievements

心臓は全身の臓器のなかで、もっともエネルギーを消費する臓器にもかかわらず、拍動する心臓でエネルギーがどのように産生・消費されているかをリアルタイムに観察する方向はなかった。我々はそれに世界で初めて成功した。今後心臓病の病態解明や新たな心臓の治療薬の開発につながる研究である。

Research Products

• [Presentation] ATP可視化マウスによる心臓の病態生理学の解析 (2017)
  • Author(s): 武蔵尭志
  • Organizer: 第243回日本循環器学会関東甲信越地方会
• [Presentation] ATP可視化マウスによる疾患病態の解明 (2016)
  • Author(s): 小板橋紀通、山本正道、磯達也、倉林正彦
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2016-06-10
  • Invited