Clarification of the role of regulatory mechanism of mitochondria DNA in heart and the application to treatment of heart failure

• Project/Area Number: 26461129
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Osaka University
• Principal Investigator: Hikoso Shungo 大阪大学, 医学系研究科, 寄附講座准教授 (30423164)
• Co-Investigator(Kenkyū-buntansha): 山口 修 大阪大学, 医学系研究科, 准教授 (90467580)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: DNase II / 心不全 / 遺伝子改変マウス / iPS細胞

Outline of Final Research Achievements

We investigated the role of DNase II, which is a responsible molecule for degradation of mitochondrial DNA, in the pathogenesis of heart failure. As for the regulatory mechanism of DNase activity, we identified that the activity is regulated via post-translational mechanism, and now we are investigating the detail. As for the therapeutic implication of DNase II for heart failure, we created cardiac-specific DNase II transgenic mice, and evaluated the phenotype. In addition, we evaluated the role of DNase II in human heart failure pathophysiology using human cardiac tissue sample of heart failure patients, and found that the expression of DNase II in failing heart is decreased compared with non-failing heart. We also found that DNA is deposited in cardiomyocytes in patients with heart failure.

Research Products

• [Journal Article] Clinical Impact of Ventricular Tachycardia and/or Fibrillation During the Acute Phase of Acute Myocardial Infarction on In-Hospital and 5-Year Mortality Rates in the Percutaneous Coronary Intervention Era (2016)
  • Author(s): 3.Masuda M, Nakatani D, Hikoso S, Suna S, Usami M, Matsumoto S, Kitamura T, Minamiguchi H, Okuyama Y, Uematsu M, Yamada T, Iwakura K, Hamasaki T, Sakata Y, Sato H, Nanto S, Hori M, Komuro I, Sakata Y
  • Journal Title: Circulation Journal Volume: 80 Issue: 7 Pages: 1539-1547
  • DOI: 10.1253/circj.CJ-16-0183
  • NAID: 130005158910
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Bcl-2-like protein 13 is a mammalian Atg32 homologue that mediates mitophagy and mitochondrial fragmentation. (2015)
  • Author(s): Murakawa T, Yamaguchi O, Hashimoto A, Hikoso S, Takeda T, Oka T, Yasui H, Ueda H, Akazawa Y, Nakayama H, Taneike M, Misaka T, Omiya S, Shah AM, Yamamoto A, Nishida K, Ohsumi Y, Okamoto K, Sakata Y, Otsu K.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 7527-7527
  • DOI: 10.1038/ncomms8527
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Big Data Clinical Research of Osaka CardioVascular Conference (OCVC)-Effort of PURSUIT-HFpEF registry (2017)
  • Author(s): 1.Hikoso S, Nakatani D, Suna S, Nakagawa A, Yasumura Y, Uematsu M, Yamada T, Dohi T, Kojima T, Matsumura Y, Sakata Y
  • Organizer: 第81回日本循環器学会学術集会
  • Place of Presentation: 金沢（日本）
  • Year and Date: 2017-03-17
  • Int'l Joint Research