Study on the molecular mechanisms and treatment for mitochondrial regulation in cardiac remodeling

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390236
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Hokkaido University
• Principal Investigator: TSUTSUI Hiroyuki 北海道大学, 大学院・医学研究科, 教授 (70264017)
• Co-Investigator(Kenkyū-buntansha): KINUGAWA Sintaro 北海道大学, 大学院・医学研究科, 助教 (60399871) ; ISHIMORI Naoki 北海道大学, 北海道大学病院, 助教 (70399848) ; MATSUI Yutaka 北海道大学, 遺伝子病制御研究所, 特任准教授 (30431381)
• Project Period (FY): 2009 – 2011
• Keywords: 心筋リモデリング / 心不全 / ミトコンドリア / DNA / 転写因子

Research Abstract

Mitochondrial oxidative stress leads to a catastrophic cycle of mitochondrial DNA damage as well as functional decline, higher oxidative stress, and cellular injury. Oxidative stress activates a broad variety of hypertrophy signaling kinases and transcription factors and mediate apoptosis. It also stimulates cardiac fibroblast proliferation and activates the matrix metalloproteinases, leading to the extracellular matrix remodeling. These cellular events are involved in the development and progression of maladaptive myocardial remodeling and failure.

Research Products

• [Journal Article] Angiotensin II-induced reduction in exercise capacity is associated with increased oxidative stress in skeletal muscle (2012)
  • Author(s): Inoue N, Kinugawa S, Suga T, Yokota T, Hirabayashi K, Kuroda S, Okita K, Tsutsui H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 302(5) Pages: H1202-10
  • Peer Reviewed
• [Journal Article] Blood Flow Restriction Exercise in Sprinters and Endurance Runners (2012)
  • Author(s): Takada S, Okita K, Suga T, Omokawa M, Morita N, Horiuchi M, Kadoguchi T, Takahashi M, Hirabayashi K, Yokota T, Kinugawa S, Tsutsui H
  • Journal Title: Med Sci Sports Exerc Volume: 44(3) Pages: 413-19
  • Peer Reviewed
• [Journal Article] Type II NKT cells stimulate diet-induced obesity by mediating adipose tissue inflammation (2012)
  • Author(s): Satoh M, Andoh Y, Clingan CS, Ogura H, Fujii S, Eshima K, Nakayama T, Taniguchi M, Hirata N, Ishimori N, Tsutsui H, Onoe K, Iwabuchi K
  • Journal Title: steatohepatitis and insulin resistance Volume: 7(2) Pages: e30568
  • Peer Reviewed
• [Journal Article] Oxidative stress in cardiac and skeletal muscle dysfunction associated with diabetes mellitus (2011)
  • Author(s): Tsutsui H, Kinugawa S, Matsushima S, Yokota T
  • Journal Title: J Clin Biochem Nutr Volume: 48 (1) Pages: 68-71
  • Peer Reviewed
• [Journal Article] High-fat diet-induced obesity and insulin resistance were ameliorated via enhanced fecal bile acid excretion in tumor necrosis factor-alpha receptor knockout mice (2011)
  • Author(s): Yamato M, Shiba T, Ide T, Seri N, Kudo W, Ando M, Yamada K, Kinugawa S, Tsutsui H
  • Journal Title: Mol Cell Biochem Volume: 359(1-2) Pages: 161-7
  • Peer Reviewed
• [Journal Article] Oxidative stress and heart failure (2011)
  • Author(s): Tsutsui H, Kinugawa S, Matsushima S
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 301 (6) Pages: H2181-90
  • Peer Reviewed
• [Journal Article] Lower aerobic capacity was associated with abnormal intramuscular energetics in patients with metabolic syndrome (2011)
  • Author(s): Yokota T, Kinugawa S, Okita K, Hirabayashi K, Suga T, Hattori M, Nakagawa Y, Oyama-Manabe N, Shirato H, Tsutsui H
  • Journal Title: Hypertens Res Volume: 34(9) Pages: 1029-34
  • Peer Reviewed
• [Journal Article] Syndecan-4 deficiency limits neointimal formation after vascular injury by regulating vascular smooth muscle cell proliferation and vascular progenitor cell mobilization (2011)
  • Author(s): Ikesue M, Matsui Y, Ohta D, Danzaki K, Ito K, Kanayama M, Kurotaki D, Morimoto J, Kojima T, Tsutsui H, Uede T
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 31(5) Pages: 1066-74
  • Peer Reviewed
• [Journal Article] Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure (2011)
  • Author(s): Ohta Y, Kinugawa S, Matsushima S, Ono T, Sobirin MA, Inoue N, Yokota T, Hirabayashi K, Tsutsui H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 300(5) Pages: H1637-44
  • Peer Reviewed
• [Journal Article] Syndecan-4 prevents cardiac rupture and dysfunction after myocardial infarction (2011)
  • Author(s): Matsui Y, Ikesue M, Danzaki K, Morimoto J, Sato M, Tanaka S, Kojima T, Tsutsui H, Uede T
  • Journal Title: Circ Res Volume: 108(11) Pages: 1328-39
  • Peer Reviewed
• [Journal Article] Effects of oral sigle-dose administration of sarpogrelate hydrochloride on saturation o2 of calf muscle during plantar flexion exercise (2010)
  • Author(s): Horiuchi M, Okita K, Takada S, Omokawa M, Suga T, Morita N, Hirabayashi K, Yokota T, Kinguawa S, Tsutsui H
  • Journal Title: Adv Exp Med Biol Volume: 662 Pages: 531-36
  • Peer Reviewed
• [Journal Article] High mitochondrial DNA copy number has detrimental effects in mice (2010)
  • Author(s): Ylikallio E, Tyynismaa H, Tsutsui H, Ide T, Suomalainen A
  • Journal Title: Hum Mol Genet Volume: 19(13) Pages: 2695-2705
  • Peer Reviewed
• [Journal Article] Overexpression of mitochondrial transcription factor A (TFAM) ameliorates delayed neuronal death due to transient forebrain ischemia in mice (2010)
  • Author(s): Hokari M, Kuroda S, Kinugawa S, Ide T, Tsutsui H, Iwasaki Y
  • Journal Title: Neuropathology Volume: 30(4) Pages: 401-7
  • Peer Reviewed
• [Journal Article] Dose effect on intramuscular metabolic stress during low-intensity resistance exercise with blood flow restriction (2010)
  • Author(s): Suga T, Okita K, Morita N, Yokota T, Hirabayashi K, Horiuchi M, Takada S, Omokawa M, Kinugawa S, Tsutsui H
  • Journal Title: J Appl Physiol Volume: 108(6) Pages: 1563-67
  • Peer Reviewed
• [Journal Article] Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice (2010)
  • Author(s): Nishioka T, Onishi K, Shimojo N, Nagano Y, Matsusaka H, Ikeuchi M, Ide T, Tsutsui H, Hiroe M, Yoshida T, Imanaka-Yoshida K
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 298(3) Pages: H1072-78
  • Peer Reviewed
• [Journal Article] Natural killer T Cells are involved in adipose tissues inflammation and glucose intolerance in diet-Induced obese mice (2010)
  • Author(s): Ohmura K, Ishimori N, Ohmura Y, Tokuhara S, Nozawa A, Horii S, Andoh Y, Fujii S, Iwabuchi K, Onoe K, Tsutsui H
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30(2) Pages: 193-99
• [Journal Article] Mitochondrial oxidative stress and dysfunction in myocardial remodelling (2009)
  • Author(s): Tsutsui H, Kinugawa S, Matsushima S
  • Journal Title: Cardiovasc Res Volume: 81(3) Pages: 449-56
  • Peer Reviewed
• [Journal Article] Oxidative stress in skeletal muscle impairs mitochondrial respiration and limits exercise capacity in type 2 diabetic mice (2009)
  • Author(s): Yokota T, Kinugawa S, Hirabayashi K, Matsushima S, Inoue N, Ohta Y, Hamaguchi S, Sobirin A, Ono T, Suga T, Kuroda S, Tanaka S, Terasaki F, Okita K, Tsutsui H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 297(3) Pages: 1069-1077
  • Peer Reviewed
• [Journal Article] Increased myocardial NAD (P) H oxidase-derived superoxide causes the exacerbation of post-infarct heart failure in type 2 diabetes (2009)
  • Author(s): Matsushima S, Kinugawa S, Yokota T, Inoue N, Ohta Y, Hamaguchi S, Tsutsui H
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 297 Pages: 409-416
  • Peer Reviewed
• [Journal Article] Intramuscular metabolism during low-intensity resistance exercise with blood flow restriction (2009)
  • Author(s): Suga T, Okita K, Morita N, Yokota T, Hirabayashi K, Horiuchi M, Takada S, Takahashi T, Omokawa M, Kinugawa S, Tsutsui H
  • Journal Title: J Appl Physiol Volume: 106 Pages: 1119-24
  • Peer Reviewed
• [Journal Article] Time-dependent changes of myocardial and systemic oxidative stress are dissociated after myocardial infarction (2009)
  • Author(s): Inoue T, Ide T, Yamato M, Yoshida M, Tsutsumi T, Andou M, Utsumi H, Tsutsui H, Sunagawa K
  • Journal Title: Free Radic Res Volume: 43(1) Pages: 37-46
  • Peer Reviewed
• [Presentation] 骨格筋からみた心不全の病態解明と治療への応用 (2011)
  • Author(s): 筒井裕之
  • Organizer: 第15回日本心不全学会学術集会
  • Place of Presentation: 鹿児島県民交流センター
  • Year and Date: 2011-10-15
• [Presentation] エビデンスに基づく慢性心不全治療 (2011)
  • Author(s): 筒井裕之
  • Organizer: 第25回日本臨床内科医学
  • Place of Presentation: 札幌コンベンションセンター
  • Year and Date: 2011-09-19
• [Presentation] 治療抵抗性心不全に挑む～エビデンスにもとづくストラテジー～ (2011)
  • Author(s): 筒井裕之
  • Organizer: 第220回日本循環器学会関東甲信越地方会
  • Place of Presentation: 東京慈恵会医科大学
  • Year and Date: 2011-06-04
• [Presentation] Mitochondrial Oxidative Stress in Cardiac Remodeling and Failure (2011)
  • Author(s): Tsutsui H
  • Organizer: International Symposium on Free Radical Research : Contributions to Medicine
  • Place of Presentation: Hyatt Regency Kyoto
  • Year and Date: 2011-01-21
• [Presentation] Mitochondrial oxidative stress in cardiac remodeling and failure (2010)
  • Author(s): Tsutsui H
  • Organizer: The Cardiovascular System Dynamics Society (CSDS)
  • Place of Presentation: グランドハイアット福岡
  • Year and Date: 2010-09-24
• [Presentation] The medical treatment of myocardial dysfunction (2010)
  • Author(s): Tsutsui H
  • Organizer: European Society of Cardiology 2010
  • Place of Presentation: Stockholm International Fairs
  • Year and Date: 2010-08-29
• [Presentation] 心不全における心腎連関 (2010)
  • Author(s): 筒井裕之
  • Organizer: 日本腎臓学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-06-18
• [Presentation] Diagnosis and management of stress-induced cardiomyopathy (2010)
  • Author(s): Tsutsui H
  • Organizer: The 74th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2010-03-05
• [Presentation] A New Therapeutic Target (2009)
  • Author(s): Tsutsui H : Insulin Resistance in Heart Failure
  • Organizer: American Heart Association Scientific Sessions 2009
  • Place of Presentation: Orange County Convention Center
  • Year and Date: 2009-11-17
• [Presentation] 心不全の発症・進展抑制を目指した高血圧治療 (2009)
  • Author(s): 筒井裕之
  • Organizer: 第57回日本心臓病学会学術集会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2009-09-19
• [Book] 心不全,糖尿病と酸化ストレス (2011)
  • Author(s): 松島将士,筒井裕之
  • Total Pages: 103-112
  • Publisher: メディカルレビュー社
• [Book] 酸化ストレス,高血圧ナビゲーター (2011)
  • Author(s): 絹川真太郎,筒井裕之
  • Total Pages: 138-139
  • Publisher: メディカルレビュー社
• [Book] ミトコンドリア(エネルギーの産生),診療に活かす心機能評価 (2010)
  • Author(s): 横田卓,筒井裕之
  • Total Pages: 26-29
  • Publisher: 羊士社
• [Book] 心不全とストレス応答,循環器ストレス学 (2010)
  • Author(s): 絹川真太郎,筒井裕之
  • Total Pages: 265-272
  • Publisher: 南山堂
• [Book] 糖尿病と心不全,Cardio Diabetic Frontier～心血管病と糖尿病を統一的に理解する新たな視点を求めて～ (2010)
  • Author(s): 絹川真太郎,筒井裕之
  • Total Pages: 62-68
  • Publisher: メディカルレビュー社
• [Book] 別冊・医学のあゆみ酸化ストレスと心血管疾患-分子機構の解明から治療への応用まで (2007)
  • Author(s): 筒井裕之(編)
  • Total Pages: 119-122
  • Publisher: 医歯薬出版株式会社
• [Remarks]
  • URL: http://cvhp.med.hokudai.ac.jp/