Role of autophagy in the progression of heart failure

• Project/Area Number: 20590865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Osaka University
• Principal Investigator: YAMAGUCHI Osamu Osaka University, 大学院・医学系研究科, 助教 (90467580)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 心不全 / オートファジー / オートファージー

Research Abstract

Constitutive autophagy is important for control of the quality of proteins and organelles to maintain cell function. We have previously reported that autophagy in the heart has a protective role in the pathogenesis of heart failure. In the present study, we monitored cardiac-specific Atg5-deficient mice. The Atg5-deficient mice began to die after the age of six months. Atg5-deficient mice exhibited severe cardiac dysfunction at the age of 10 months. Ultrastructural analysis revealed a disorganized sarcomere structure and collapsed mitochondria in Atg5-deficient mice. These results suggest that continuous constitutive autophagy plays a crucial role in maintaining cardiac structure and function.

Research Products

• [Journal Article] Inhibition of autophagy in the heart induces age-relacardiomyopathy. (2010)
  • Author(s): 種池学, 山口修, 他15名
  • Journal Title: Autophag
  • Peer Reviewed
• [Journal Article] Activation of MTK1/MEKK4 inducescardiomocyte death and heart failure. (2010)
  • Author(s): 溝手勇, 山口修, 他11名
  • Journal Title: Mol Cell Cardiol. 48巻 Pages: 302-309
  • Peer Reviewed
• [Journal Article] Inhibition of autophagy in the heart induces age-related cardiomyopathy (2010)
  • Author(s): Manabu Taneike, Osamu Yamaguchi, 他
  • Journal Title: Autophagy Volume: 6 Pages: 600-606
  • Peer Reviewed
• [Journal Article] Novel in vivo tool to evaluate autophagic activity in the heart (2010)
  • Author(s): Osamu Yamaguchi, 他
  • Journal Title: Circulation Journal 74 Pages: 49-50
  • NAID: 10025941131
• [Journal Article] Activation of MTK1/MEKK4 induces cardiomyocyte death and heart failure (2010)
  • Author(s): Isamu Mizote, 他
  • Journal Title: Journal of Molecular and Cellular Cardiology 48 Pages: 302-309
  • Peer Reviewed
• [Journal Article] I{kappa}B kinase {beta}/nuclear factor {kappa}B signaling pahway protects the heart from hemodynamic stress mediated by the regulation of manganese superoxide dismutase expression. (2009)
  • Author(s): 彦惣俊吾, 山口修, 他15名
  • Journal Title: Circ Res. 105巻 Pages: 70-79
  • Peer Reviewed
• [Journal Article] Downregulation of chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes. (2009)
  • Author(s): 大宮茂幹, 彦惣俊吾, 山口修(5番目), 他12名
  • Journal Title: J Mol Cell Cardiol 46巻 Pages: 59-66
  • Peer Reviewed
• [Journal Article] The I{kappa}B kinase {beta}/nuclear factor {kappa}B signaling pathway protects the heart from hemodynamic stress mediated by the regulation of manganese superoxide dismutase expression (2009)
  • Author(s): Shungo Hikoso, 他
  • Journal Title: Circulation Research 105 Pages: 70-79
  • Peer Reviewed
• [Journal Article] Downregulation of ferritin heavy chain increases labile iron pool, oxidative stress and cell death in cardiomyocytes (2009)
  • Author(s): Shigemiki Omiya, 他
  • Journal Title: Journal of Molecular and Cellular Cardiology 46 Pages: 59-66
  • Peer Reviewed
• [Journal Article] The role of autophagy in the heart (2009)
  • Author(s): Kazuhiko Nishida, 他
  • Journal Title: Cell Death and Differentiation 16 Pages: 31-38
  • Peer Reviewed
• [Journal Article] Qualitative and quantitative changes in coronary plaqueassociated with atorvastatin therapy. (2009)
  • Author(s): Atsushi Hirayama, 他
  • Journal Title: Circulation Journal (In press)
  • Peer Reviewed
• [Journal Article] Reductin in hemoglobin-oxygen affinity results in the improvement of exercise with chronic heart failure. (2008)
  • Author(s): 渡部徹也, 武田理宏, 大宮茂幹, 彦惣俊吾, 山口修, 他14名
  • Journal Title: J Am Coll Cardiol. 52巻 Pages: 779-786
  • Peer Reviewed
• [Journal Article] Apoptosis signal-regulating kinase 1 (ASKl)/p38 signaling pathway negatively regulates physiological hypertrophy (2008)
  • Author(s): Masayuki Taniike, 他
  • Journal Title: Circulation 117 Pages: 545-552
  • Peer Reviewed
• [Journal Article] Reduction in hemoglobin-oxygen affinity results in the improvement ofexercise capacity in mice with chronic heart failure (2008)
  • Author(s): Tetsuya Watanabe, 他
  • Journal Title: Journal of American College of Cardiology 52 Pages: 779-786
  • Peer Reviewed
• [Journal Article] Crosstalk between autophagy and apoptosis in heart disease (2008)
  • Author(s): Kazuhiko Nishida, 他
  • Journal Title: Circulation Research 103 Pages: 343-351
  • Peer Reviewed
• [Journal Article] Cardiac overexpression of hormone-sensitive lipase inhibits myocardial steatosis and fibrosis in streptozotocin diabetic mice (2008)
  • Author(s): Masami Ueno, 他
  • Journal Title: American Journal of Physiology Endocrinology and Metabolism 294
  • Peer Reviewed
• [Presentation] The Degradation System in Cardiomyopathy (2011)
  • Author(s): 山口修
  • Organizer: 第75回日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2011-03-18
• [Presentation] Mitochondrial Permeability Transition and Non-qpoptotic Cell Death. (2010)
  • Author(s): 山口修
  • Organizer: Basic Cardiovascular Sciences 2010 Scientific Sessions.
  • Place of Presentation: Rancho Mirage(米国)
  • Year and Date: 2010-07-20
• [Presentation] Mitochondrial Permeability Transition and Non-apoptotic Cell Death (2010)
  • Author(s): Osamu Yamaguchi
  • Organizer: Basic Cardiovascular Sciences 2010 Scientific Sessions
  • Place of Presentation: Rancho Mirage, CA (USA)(招待講演)
  • Year and Date: 2010-07-20
• [Presentation] Essential Role of Autophagy to Maintain Cardiac Function in Response to Hemodynamic Stress and in Senescence. (2009)
  • Author(s): 山口修
  • Organizer: 第26回国際心臓研究会日本部会
  • Place of Presentation: 札幌
  • Year and Date: 2009-12-05
• [Presentation] Essential Role of Autophagy to Maintain Cardiac Function in Response to Hemodynamic Stress and in Senescence (2009)
  • Author(s): 山口修
  • Organizer: 第26回国際心臓研究会日本部会
  • Place of Presentation: 札幌・北海道大学
  • Year and Date: 2009-12-05
• [Presentation] Non-apoptotic Cardiomyocyte Death as a Cause of Cardiac Remodeling. (2009)
  • Author(s): 山口修
  • Organizer: 第73回日本循環器学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Cell death and cardiac remodeling (2008)
  • Author(s): 山口修
  • Organizer: 第25回國際心臓研究会日本部会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-05
• [Presentation] Cell death and cardiac remodeling (2008)
  • Author(s): 山口 修
  • Organizer: 第2 5回国際心臓研究会日本部会
  • Place of Presentation: 横浜
  • Year and Date: 2008-12-05