Role of ER oxidoreductin-1 in cardiovascular remodeling

• Project/Area Number: 24591096
• 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: Osaka University
• Principal Investigator: MINAMINO TETSUO 大阪大学, 医学(系)研究科(研究院), 准教授 (30379234)
• Co-Investigator(Kenkyū-buntansha): HIGO Schuichiro 大阪大学, 大学院医学系研究科, 助教 (00604034) ; HAO Hiroyuki 兵庫医科大学, 医学系研究科, 准教授 (40393243) ; ASANO Yoshihiro 大阪大学, 大学院医学系研究科, 助教 (60527670) ; SANADA Shoji 大阪大学, 保健センター, 助教 (70593797) ; TSUKAMOTO Osamau 大阪大学, 大学院医学系研究科, 特任研究員 (80589151)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 小胞体ストレス / 腹部大動脈瘤 / 低酸素 / ジスルフィド結合

Outline of Final Research Achievements

Hypoxic stimuli play important roles in the development of cardiovascular diseases such as ischemic heart disease, atherosclerosis. In the present study, to clarify the role of ER oxidoreductin-1 (Ero1), a major ER oxidase, in the development of abdominal aortic aneurysm, we have tried and succeeded to create Ero1 knockout mice by ES trap method. Interestingly, we found that Ero1 expression increased in human samples from abdominal aortic aneurysm. We also found that continuous infusion of angiotensin II induced abdominal aortic aneurysm in Ero1 knockout, but not normal, mice, suggesting that Ero1 plays an important role in the development of abdominal aortic aneurysm.

Research Products

• [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5. (2015)
  • Author(s): Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
  • Journal Title: Nat Commun. Volume: 6 Issue: 1 Pages: 6137-6137
  • DOI: 10.1038/ncomms7137
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase (2015)
  • Author(s): T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
  • Journal Title: Proc. Nat. Acad. Sci. U.S.A. Volume: 112 Issue: 5 Pages: 1553-1558
  • DOI: 10.1073/pnas.1419767112
  • Peer Reviewed / Open Access
• [Journal Article] Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: Role of NO. (2014)
  • Author(s): Asanuma H, Sanada S, Asakura M, Asano Y, Kim J, Shinozaki Y, Mori H, Minamino T, Takashima S,Kitakaze M.
  • Journal Title: Hypertens Res. Volume: 37(8) Issue: 8 Pages: 716-23
  • DOI: 10.1038/hr.2014.70
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Evaluation of intra-mitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation (2013)
  • Author(s): Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Tkafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y and Takashima S
  • Journal Title: PNAS Volume: 111 Issue: 1 Pages: 273-278
  • DOI: 10.1073/pnas.1318547111
  • Peer Reviewed / Open Access
• [Journal Article] Decreased Mortality Associated with Statin Treatment in Patients with Acute Myocardial Infarction and Lymphotoxin- C804A Polymorphism. (2013)
  • Author(s): Suna Shinichiro
  • Journal Title: Atherosclerosis Volume: 227 Issue: 2 Pages: 373-379
  • DOI: 10.1016/j.atherosclerosis.2013.01.020
  • Peer Reviewed
• [Journal Article] Treatment of cerebral ischemia-reperfusion injury with PEGylated liposomes encapsulating FK506. (2013)
  • Author(s): Ishii T, Asai T, Oyama D, Agato Y, Yasuda N, Fukuta T, Shimizu K, Minamino T, Oku N.
  • Journal Title: FASEB J. Volume: 27 Issue: 4 Pages: 1362-1370
  • DOI: 10.1096/fj.12-221325
  • Peer Reviewed
• [Journal Article] Dipeptidyl-Peptidase IV Inhibition Improves Pathophysiology of Heart Failure and Increases Survival Rate in Pressure-Overloaded Mice (2013)
  • Author(s): Takahashi A, Asakura M, Ito S, Min KD, Shindo K, Yan Y, Liao Y, Yamazaki S, Sanada S, Asano Y, Ueda H, Takashima S, Minamino T, Asanuma H, Mochizuki N, Kitakaz M
  • Journal Title: Am J Phyisol Volume: In press
  • Peer Reviewed
• [Journal Article] Liposomal amiodarone augments anti-arrhythmic effects and reduces hemodynamic adverse effects in an ischemia/reperfusion rat model. (2013)
  • Author(s): Takahama H, Shigematsu H, Asai T, Matsuzaki T, Sanada S, Fu HY, Okuda K, Yamato M, Asanuma H, Asano Y, Asakura M, Oku N, Komuro I, Kitakaze M, Minamino T.
  • Journal Title: Cardiovasc Drugs Ther. Volume: 27 Issue: 2 Pages: 125-132
  • DOI: 10.1007/s10557-012-6437-6
  • Peer Reviewed
• [Journal Article] Development of anti-HB-EGF immunoliposomes for the treatment of breast cancer. (2012)
  • Author(s): K. Nishikawa, T. Asai, H. Shigematsu, K. Shimizu, H. Kato, Y. Asano, S. Takashima, E. Mekada, N. Oku, T. Minamino
  • Journal Title: J. Control. Release Volume: 160 Issue: 2 Pages: 274-280
  • DOI: 10.1016/j.jconrel.2011.10.010
  • Peer Reviewed
• [Journal Article] Amelioration of cerebral ischemia-reperfusion injury based on liposomal drug delivery system with asialo-erythropoietin (2012)
  • Author(s): T.Ishii, T.Asai, D.Oyama, T.Fukuta, N.Yasuda, K.Shimizu, T.Minamino, N.Oku
  • Journal Title: Journal of Controlled Release Volume: (In press) Issue: 1 Pages: 81-87
  • DOI: 10.1016/j.jconrel.2012.02.004
  • Peer Reviewed
• [Presentation] アカデミア創薬：院内GMPリポソームを用いた急性心筋梗塞に対する新しい治療薬の開発 (2015)
  • Author(s): 南野哲男
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 東京（慶応義塾大学薬学部芝共立キャンパス）
  • Year and Date: 2015-07-30 – 2015-07-31
• [Presentation] シンポジウム ＜新たに見えてきた慢性心不全治療の標的 Novel treatment targets of heart failure＞ Ablation of C/EBP homologous protein attenuates endoplasmic reticulum-mediated apoptosis and cardiac dysfunction induced by pressure overload (2013)
  • Author(s): 南野哲男
  • Organizer: 第76回日本循環器学会総会・学術集会・
  • Place of Presentation: 横浜
  • Invited
• [Presentation] シンポジウム2 ＜小胞体ストレスと活性酵素ストレスのクロストーク＞心血管リモデリングにおける小胞体ストレス応答の役割解明 (2012)
  • Author(s): 南野哲男
  • Organizer: 第12回日本NO学会学術集会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Development of Novel Therapy for Autoimmune Myocarditis with Nanotechnology
  • Author(s): 富 海英、南野哲男
  • Organizer: 日本心不全学会 YIA
  • Place of Presentation: 埼玉県大宮市
• [Presentation] Academic Drug Development for Treatment of Acute Myocardial Infarction Using Nano-sized Liposomes
  • Author(s): 南野哲男
  • Organizer: 日本循環器学会学術集会総会
  • Place of Presentation: 東京
• [Book] 小胞体ストレスと心臓病 (2013)
  • Author(s): 南野哲男、小室一成
  • Total Pages: 4
  • Publisher: ニューサイエンス社
• [Patent(Industrial Property Rights)] 炎症性疾患治療用医薬組成物 (2014)
  • Inventor(s): 南野哲男
  • Industrial Property Rights Holder: 南野哲男
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-23
  • Overseas