Anti-remodeling effect of mitochondrial DNA; A novel approach for the treatment of heart failure using recombinant TFAM

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyushu University
• Principal Investigator: IDE Tomomi 九州大学, 医学研究院, 講師 (90380625)
• Project Period (FY): 2011 – 2013
• Keywords: ミトコンドリア / 活性酵素 / 心肥大

Research Abstract

The overexpression of mitochondrial transcription factor A (TFAM) attenuates the decrease in mtDNA copy number after myocardial infarction, ameliorates pathological hypertrophy, and markedly improves survival. However, non-transgenic strategy to increase mtDNA for the treatment of pathological hypertrophy remains unknown. We produced recombinant human TFAM protein (rhTFAM). rhTFAM rapidly entered into mitochondria of cultured cardiac myocytes. rhTFAM increased mtDNA and abolished the activation of nuclear factor of activated T cells (NFAT), which is well known to activate pathological hypertrophy. rhTFAM attenuated
subsequent morphological hypertrophy of myocytes as well. rhTFAM would be an attractive molecule in attenuating cardiac pathological hypertrophy.

Research Products

• [Journal Article] Cardiac phase-targeted dynamic load on left ventricle differentially regulates phase-sensitive gene expression s and pathway activation (2013)
  • Author(s): Onitsuka K, Ide T, Arai S, Hata Y, Murayama Y, Hosokawa K, Sakamoto T, Tobushi T, Sakamoto K, Fujino T, Sunagawa K
  • Journal Title: J Mol Cell Cardiol Volume: 64C Pages: 30-38
• [Journal Article] The overexpression of Twinkle helicase ameliorates the progression of cardiac fibrosis and heart failure in pressure overload model in mice (2013)
  • Author(s): Tanaka A, Ide T, Fujino T, Onitsuka K, Ikeda M, Takehara T, Hata Y, Ylikallio E, Tyynismaa H, Suomalainen A, Sunagawa K
  • Journal Title: PLoS One Volume: 8 Pages: e67642
• [Journal Article] Recombinant mitochondrial transcription factor A protein inhibits nuclear factor of activated T cells signaling and attenuates pathological hypertrophy of cardiac myocytes (2012)
  • Author(s): Fujino T, Ide T, Yoshida M, Onitsuka K, Tanaka A, Hata Y, Nishida M, Takehara T, Kanemaru T, Kitajima N, Takazaki S, Kurose H, Kang D, Sunagawa K
  • Journal Title: Mitochondrion Volume: 12 Pages: 449-458
• [Presentation] The Overexpression of Mitochondrial Transcription Factor A Attenuates Mitochondrial Reactive Oxygen Species Generation and Inhibits Pathological Remodeling in Cardiac Myocytes (2013)
  • Author(s): Fujino T, Ide T, Ikeda M, Onitsuka K, Hata Y, Takehara T, Sakamoto K, Tobushi T, Saku K, Sunagawa K
  • Organizer: 日本心不全学会
  • Place of Presentation: (Journal of Cardiac Failure 2012; 18 (10S): S170)
  • Year and Date: 20131000
• [Presentation] The Increase of Mitochondrial DNA Copy Number Attenuates Eccentric Cardiac Remodeling in Volume Overload Model Circ J. 77(SupplI): 425 (2013)
  • Author(s): Masataka Ikeda ,Tomomi Ide ,Takeo Fujino ,Ken Onitsuka ,Tomoyuki Tobushi ,Kazuo Sakamoto ,Keita Saku ,Takamori Kakino ,Henna Tyynismaa ,Hiroyuki Tsutsui ,Anu Suomalainen ,Kenji Sunagawa
  • Organizer: 2013第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20130315-17
• [Presentation] Increased Mitochondrial DNA Copy Number Attenuates Excessive Mitochondrial Reactive Oxygen Species and Inhibits NFAT Signaling in Cardiac Myocytes. Circulation Journal 2013; 77 (Suppl. I): I-952 (2013)
  • Author(s): Fujino T, Ide T, Ikeda M, Onitsuka K, Hata Y, Takehara T, Sakamoto K, Tobushi T, Saku K, Kakino T, Sunagawa K
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20130315-17
• [Presentation] The increase of Mitochondrial DNA Copy Number Attenuates Eccentric Cardiac Remodeling in Volume Overload Model (2012)
  • Author(s): Masataka Ikeda, Tomomi Ide, Takeo Fujino, Yuko Hata, Takako Takehara, Ken Onitsuka, Tomoyuki Tobushi, Kazuo Sakamoto, Keita Saku, Takamori Kakino, Kenji Sunagawa
  • Organizer: 第29回国際心臓研究会日本部会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121026-27
• [Presentation] The Increase of Mitochondrial DNA Copy Number Attenuates Mitochondrial Reactive Oxygen Species Generation and Inhibits Pathological Remodeling in Cardiac Myocytes (2012)
  • Author(s): Fujino T, Ide T, Ikeda M, Onitsuka K, Hata Y, Takehara T, Sakamoto K, Tobushi T, Saku K, Kakino T, Sunagawa K
  • Organizer: 第29回国際心臓研究会日本部会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121026-27
• [Presentation] Phase Targeted Dynamic Load of Left Ventricle Induces Distinct Phase Sensitive Gene Expressions and Pathway Activation (2012)
  • Author(s): Ken Onitsuka, Tomomi Ide, Shinobu Arai, Yuko Hata, Takako Takehara, Yoshinori Murayama, Kazuo Sakamoto, Tomoyuki Tobushi, Takeo Fujino, Keita Saku, Masataka Ikeda, Takamori Kakino, Kenji Sunagawa
  • Organizer: 第29回国際心臓研究会日本部会総会
  • Place of Presentation: 福岡
  • Year and Date: 20121026-27