Cardiac Autophagy and Mitochondria in the Progress of Heart Failure

2011 Fiscal Year Final Research Report

• Project/Area Number: 21590939
• 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: Meiji University of Integrative Medicine (2010-2011); Kyoto Prefectural University of Medicine (2009)
• Principal Investigator: IWAI-KANAI Eri 明治国際医療大学, 医学教育研究センター, 教授 (20372584)
• Co-Investigator(Kenkyū-buntansha): MATOBA Satoaki 京都府立医科大学, 医学研究科, 助教 (10305576)
• Project Period (FY): 2009 – 2011
• Keywords: 心不全 / ミトコンドリア / 細胞死 / オートファジー

Research Abstract

Using a new method for cardiac autophagy which was established by us, we examined the mechanism of cardiac repair in the progress of heart failure. Cardiac autophagy was accelerated in the early phase of heart failure, which was key for cardiac protection. In the heart of metabolic disorder, ischemia, or anti-cancer drug, the control of cardiac autophagy was impaired and p53-TIGAR pathway acted as a critical role for cardiac cellular fate.

Research Products

• [Journal Article] Prognostic impact of systolic blood pressure at admission on in-hospital outcome after primary percutaneous coronary intervention for acute myocardial infarction (2012)
  • Author(s): Shiraishi J, Kohno Y, Sawada T, Hashimoto S, Ito D, Kimura M, Matsui A, Yokoi H, Arihara M, Irie H, Hyogo M, Shima T, Nakamura T, Matoba S, Yamada H, Matsumuro A, Shirayama T, Kitamura M, Furukawa K, Matsubara H.
  • Journal Title: J Cardiol
• [Journal Article] p53 promotes cardiac dysfunction in diabetic mellitus caused by excessive mitochondrial respiration-mediated reactive oxygen species generation and lipid accumulation (2012)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Ikeda K, Okigaki M, Adachi S, Tanaka H, Takamatsu T, Matsubara H.
  • Journal Title: Circ Heart Fail Volume: 5(1) Pages: 106-15
• [Journal Article] p53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia (2012)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Nakamura H, Kimata M, Nakaoka M, Katamura M, Okawa Y, Ariyoshi M, Mita Y, Ikeda K, Ueyama T, Okigaki M, Matsubara H.
  • Journal Title: J Mol Cell Cardiol Volume: 52(1) Pages: 175-84
• [Journal Article] Loss of bcl-2 during the senescence exacerbates the impaired angiogenic functions in endothelial cells by deteriorating the mitochondrial redox state (2011)
  • Author(s): Uraoka M, Ikeda K, Kurimoto-Nakano R, Nakagawa Y, Koide M, Akakabe Y, Kitamura Y, Ueyama T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Hypertension Volume: 58(2) Pages: 254-63
• [Journal Article] Early inflammatory reactions in atherosclerosis are induced by proline-rich tyrosine kinase/reactive oxygen species-mediated release of tumor necrosis factor-alpha and subsequent activation of the p21Cip1/Ets-1/p300 system (2011)
  • Author(s): Katsume A, Okigaki M, Matsui A, Che J, Adachi Y, Kishita E, Yamaguchi S, Ikeda K, Ueyama T, Matoba S, Yamada H, Matsubara H.
  • Journal Title: Arterioscler Thromb Vasc Biol
• [Journal Article] p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic stress (2010)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Okigaki M, Ikeda K, Tatsumi T, Matsubara H.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 299(6) Pages: 1908-16
• [Journal Article] Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo (2010)
  • Author(s): Nakagawa Y, Ikeda K, Akakabe Y, Koide M, Uraoka M, Yutaka KT, Kurimoto-Nakano R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30(10) Pages: 1908-15
• [Journal Article] AMI-Kyoto Multi-Center Risk Study Group. Clinical manifestations and effects of primary percutaneous coronary intervention for patients with delayed pre-hospital time in acute myocardial infarction (2010)
  • Author(s): Nomura T, Tatsumi T, Sawada T, Kojima A, Urakabe Y, Enomoto-Uemura S, Nishikawa S, Keira N, Nakamura T, Matoba S, Yamada H, Matsumuro A, Shirayama T, Shiraishi J, Kohno Y, Kitamura M, Furukawa K, Matsubara H
  • Journal Title: J Cardiol Volume: 56(2) Pages: 204-10
• [Journal Article] Granulocyte colony-stimulating factor protects cardiac mitochondria in the early phase of cardiac injury (2009)
  • Author(s): Hiraumi Y, Iwai-Kanai E, Baba S, Yui Y, Kamitsuji Y, Mizushima Y, Matsubara H, Watanabe M, Watanabe K, Toyokuni S, Matsubara H, Nakahata T, Adachi S.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 296(3) Pages: 23-32
• [Journal Article] Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system (2009)
  • Author(s): Uraoka M, Ikeda K, Nakagawa Y, Koide M, Akakabe Y, Nakano-Kurimoto R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Biochem Biophys Res Commun Volume: 390(4) Pages: 1202-7
• [Journal Article] Pressure-mediated hypertrophy and mechanical stretch induces IL-1 release and subsequent IGF-1 generation to maintain compensative hypertrophy by affecting Akt and JNK pathways (2009)
  • Author(s): Honsho S, Nishikawa S, Amano K, Zen K, Adachi Y, Kishita E, Matsui A, Katsume A, Yamaguchi S, Nishikawa K, Isoda K, Riches DW, Matoba S, Okigaki M, Matsubara H.
  • Journal Title: Circ Res Volume: 105(11) Pages: 1149-58
• [Journal Article] Replicative senescence of vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transition (2009)
  • Author(s): Nakano-Kurimoto R, Ikeda K, Uraoka M, Nakagawa Y, Yutaka K, Koide M, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 297(5) Pages: 1673-84
• [Journal Article] Apoptosis regulator through modulating IAP expression(ARIA) controls the PI3K/Akt pathway in endothelial and endothelial progenitor cells
  • Author(s): Koide M, Ikeda K, Akakabe Y, Kitamura Y, Ueyama T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Proc Natl Acad Sci USA.
• [Journal Article] LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated with cytoprotection
  • Author(s): Yuan H, Perry CN, Huang C, Iwai-Kanai E, Carreira RS, Glembotski CC, Gottlieb RA.
• [Presentation] Granulocyte colony-stimulating factor(G-CSF) protects cardiac myocytes against doxorubicin induced injury via the stabilization of MDM2 (2012)
  • Author(s): Mita Y, Iwai-Kanai E, Matoba S, Nakaoka M, Kimata M, Nakamura H, Hoshino A, Katamura M, Okawa Y, Matsubara H.
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120317-19
• [Presentation] Curcumin protect mice heart against doxorubicin induced cardiomyopathy thorough the induction of autophagy (2012)
  • Author(s): Katamura M, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Nakaoka M, Hoshino A, Okawa Y, Mita Y, Matsubara H.
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120317-19
• [Presentation] P53 promotes cardiac aging through the inhibition of parkin mediated mitochondrial quality control (2011)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Nakaoka M, Katamura M, Mita Y, Matsubara H.
  • Organizer: The 84th Scientific Sessions of the American Heart Association
  • Place of Presentation: Orlando, U. S. A
  • Year and Date: 20111112-16
• [Presentation] P53-TIGAR axis attenuates mitophagy to exacerbate cardiac damage after ischemia (2011)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Katamura M, Mita Y, Matsubara H.
  • Organizer: The 84th Scientific Sessions of the American Heart Association
  • Place of Presentation: Orlando, U. S. A
  • Year and Date: 20111112-16
• [Presentation] Mitochondrial Respiration-Mediated ROS Generation and Lipid Accumulation (2011)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Katamura M, Adachi S, Matsubara H.
  • Organizer: The 84th Scientific Sessions of the American Heart Association
  • Place of Presentation: Orlando, U. S. A
  • Year and Date: 20111112-16
• [Presentation] G-CSFによる心筋保護効果と抗がん作用への影響 (2011)
  • Author(s): 三田雄一郎、的場聖明、松原弘明、木股正樹、中村英夫、星野温、中岡幹彦、片村真紀、大川善文、三田雄一郎、金井恵理
  • Organizer: 第20回日本Cell Death学会
  • Place of Presentation: 東京
  • Year and Date: 20110729-30
• [Presentation] ドキソルビシン心筋障害に対しクルクミンは心筋保護作用を示す (2011)
  • Author(s): 片村真紀、的場聖明、松原弘明、木股正樹、中村英夫、中岡幹彦、星野温、大川善文、三田雄一郎、金井恵理
  • Organizer: 第20回日本Cell Death学会
  • Place of Presentation: 東京
  • Year and Date: 20110729-30
• [Presentation] p53-Mediated Decrease in ROS Signal Reduces Mitophagy via Inactivation of Bnip3 to Aggravate Cardiac Damage After Ischemic Injury (2010)
  • Author(s): Hoshino A, Matoba S, Iwai-Kanai E, Kimata M, Nakamura H, Nakaoka M, Katamura M, Mita Y, Matsubara H.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101114-16
• [Presentation] p53-mediated Acceleration of Mitochondrial Oxygen Consumption Promotes Lipotoxicity via SCO2 in Diabetic Mice (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Katamura M, Adachi S, Matsubara H.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101114-16
• [Presentation] Imaging oxidative stress in unstable atherosclerotic plaque with iodine-125-labeled 4-hydroxy-2-nonenal in vivo (2010)
  • Author(s): Doue T, Iwai-Kanai E, Ohtsuki K, Matoba S, Ogawa K, Matsubara H.
  • Organizer: American Heart Association Scientific Sessions
  • Place of Presentation: Chicago, Illinois, USA
  • Year and Date: 20101114-16
• [Presentation] G-CSF protects cardiac mitochondria (2010)
  • Author(s): Iwai-Kanai E. Hiraumi Y, Matoba S, Adachi S, Matsubara H
  • Organizer: Mitochondrial Conference of NIH
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20101100
• [Presentation] 心不全の進展における心筋細胞死とオートファジーによる心保護のメカニズム (2010)
  • Author(s): Nakaoka M, Iwai-Kanai E, et. al.
  • Organizer: 第18回日本Cell Death学会
  • Place of Presentation: 長崎
  • Year and Date: 20100801-02
• [Presentation] 心筋虚血におけるp53と心筋 (2010)
  • Author(s): Hoshino A, Iwai-Kanai E, et. al
  • Organizer: 第18回日本Cell Death学会
  • Place of Presentation: 長崎
  • Year and Date: 20100801-02
• [Presentation] p53発現抑制におけるオートファジーを介した虚血心筋保護効果 (2010)
  • Author(s): 星野温、的場聖明、金井恵理、中岡幹彦、木股正樹、中村英夫、片村真紀、堂上友紀、松原弘明
  • Organizer: 第19回日本cell death学会
  • Place of Presentation: 名古屋
  • Year and Date: 20100800
• [Presentation] 交感神経刺激による心筋アポトーシス、オートファジーの制御 (2010)
  • Author(s): 中岡幹彦、金井恵理、的場聖明、木股正樹、中村英夫、星野温、片村真紀、堂上友紀、松原弘明
  • Organizer: 第19回日本cell death学会
  • Place of Presentation: 名古屋
  • Year and Date: 20100800
• [Presentation] G-CSF protects cardiac myocytes in the progress of heart failure (2010)
  • Author(s): Iwai-Kanai E
  • Organizer: Protein Peptide Conference
  • Place of Presentation: Beijing, China
  • Year and Date: 20100521-23
• [Presentation] 新型インフルエンザAH1pdmの動向と心筋炎 (2010)
  • Author(s): Iwai-Kanai E
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] The Role of Autophagy in Diastolic Heart Failing State of Heart Failure (2010)
  • Author(s): Iwai-Kanai E, Hiraumi Y, Matoba S, Adachi S, Matsubara H.
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] p53 and SCO2(Synthesis of Cytochrome c Oxidase 2) Augment the Progression of Diabetic Cardiomyopathy (2010)
  • Author(s): Nakamura H, Matoba S, Iwai-Kanai E, Kimata M, Hoshino A, Katamura M, Adachi S, Matsubara H.
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] Hypoxia-Induced p53 Deteriorates Cardiac Energetics and Apoptotic Cell Death via TIGAR(TP53-Induced Glycolysis and Apoptosis Regulator) (2010)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Okigaki M, Ikeda K, Tatsumi T, Matsubara H.
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] Differential roles of Akt and Extracellular signal-regulated kinase signaling pathways on autophagy during alpha1-adrenergic agonist mediated cardioprotection (2010)
  • Author(s): Nakaoka M, Iwai-Kanai E, Matoba S, Kimata M, Nakamura H, Hoshino A, Katamura M, Adachi S, Matsubara H.
  • Organizer: 第74回日本循環器学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 20100300
• [Presentation] 高齢予備世代の高血圧患者とMRI集団健診を用いたハイリスクアプローチ:京都府乙訓地域における疫学研究 (2009)
  • Author(s): Iwai-Kanai E, et. al.
  • Organizer: 第32回日本高血圧学会
  • Place of Presentation: 大津
  • Year and Date: 20091002-03
• [Presentation] 交感神経の亢進による心筋オートファジーの誘導 (2009)
  • Author(s): Nakaoka M, Iwai-Kanai E, et. al
  • Organizer: 第32回日本高血圧学会
  • Place of Presentation: 大津
  • Year and Date: 20091002-03
• [Presentation] P53/TIGARはグルコース代謝を抑えて心筋アポトーシスを誘導する (2009)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, et. al.
  • Organizer: 第32回日本高血圧学会
  • Place of Presentation: 大津
  • Year and Date: 20091002-03
• [Book] 心不全.プチナース疾患別看護過程 (2012)
  • Author(s): 麹谷康子、金井恵理
  • Publisher: 照林社
• [Book] 肥大型心筋症.最新治療「循環器疾患」 (2012)
  • Author(s): 金井恵理、松森昭
  • Publisher: 文光堂
• [Book] 心臓MRS.磁気共鳴スペクトルの医学応用-基礎から臨床までー (2012)
  • Author(s): 金井恵理
  • Publisher: 株インナービジョン
• [Book] 心筋梗塞.プチナース疾患別看護過程 (2011)
  • Author(s): 岡田朱美、金井恵理
  • Publisher: 照林社
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/k/med2/group/cardio/kenkyu-07.html