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2018 Fiscal Year Annual Research Report

Study of Molecular Mechanisms of Heart Failure

Research Project

Project/Area Number 16K09421
Research InstitutionNiigata University

Principal Investigator

田中 孔明  新潟大学, 医歯学総合研究科, 客員研究員 (70572725)

Co-Investigator(Kenkyū-buntansha) 南野 徹  新潟大学, 医歯学系, 教授 (90328063)
Project Period (FY) 2016-04-01 – 2019-03-31
Keywords心不全 / ミトコンドリア
Outline of Annual Research Achievements

心不全はあらゆる心臓病の終末像であり、癌とともに最も予後不良な疾患群の一つである。また、社会の高齢化や、食生活・生活様式の変化による肥満関連疾患(高血圧症、糖尿病など)の増加の影響は大きく、日本の心不全患者は、2035年には130万人に到達すると予測されている。しかしながら、心不全の病態生理はいまだに不明な点が多く、有効な治療法も確立されていない。そこで、本研究では、網羅的代謝物質解析技術(メタボロミクス)を用い、臨床的指標と比較検討することにより、心不全患者(特に、治療抵抗性患者)における代謝リモデリングの解明を目指す。それにより、心血管疾患の発症と進展に関与する未知の代謝メカニズムを明らかにし、新たな病態解明、それらを標的とする新しい治療戦略の基盤の構築、病状把握のためのバイオマーカーを確立する。また、その結果を遺伝子改変マウスの作成等、基礎研究へ還元することにより、より深い病態解明につなげることを目標とする。
心血管カテーテル検査を施行し、その際に計4ヵ所(動脈: 末梢動脈血・大動脈血、静脈: 末梢静脈血・冠状静脈洞血)から血液検体を採取、後日にこれらの検体を用いてメタボロミクスによる代謝リモデリングの解析を行ったところ、ミトコンドリア代謝に関するメタボライトが治療抵抗性心不全患者で変化していた。並行して心筋生検サンプルを用いたトランスクリプトーム解析を行ったところ、ミトコンドリアのフージョンに関与する分子(Mfn1)の発現が治療抵抗性心不全患者で低下していることがわかった。マウスモデルを用いた検討から、Mfn1が心不全治療反応性に関連する分子であることが明らかとなった。

  • Research Products

    (50 results)

All 2019 2018 Other

All Journal Article (18 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 18 results,  Open Access: 18 results) Presentation (17 results) (of which Int'l Joint Research: 10 results,  Invited: 17 results) Book (13 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Gamma-aminobutyric acid signaling in brown adipose tissue promotes systemic metabolic derangement in obesity.2018

    • Author(s)
      Ikegami R, Shimizu I, Sato T, Yoshida Y, Hayashi Y, Suda Ma, Katsuumi G, Li J, Wakasugi T, Minokoshi Y, Okamoto S, Hinoi E, Nielsen S, Zenius Jespersen N, Scheele C, Soga T, Minamino T
    • Journal Title

      Cell Rep.

      Volume: 24 Pages: 2827-2837

    • DOI

      DOI: 10.1016/j.celrep.2018.08.024

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical predictors of recurrent ventricular arrhythmias in secondary prevention implantable cardioverter defibrillator recipients with coronary artery disease-Lower left ventricular ejection fraction and incomplete revascularization.2018

    • Author(s)
      Takano T, Tanaka K, Ozaki K, Sato A, Iijima K, Yanagawa T, Izumi D, Ozawa T, Fuse K, Sato M, Tanabe N, Minamino T.
    • Journal Title

      Circ J.

      Volume: 82 Pages: 3037-3043.

    • DOI

      DOI: 10.1253/circj.CJ-18-0646

    • Peer Reviewed / Open Access
  • [Journal Article] Dynamic left ventricular outflow tract obstruction complicated with takotsubo cardiomyopathy: The acute phase of takotsubo cardiomyopathy manifests latent left ventricular outflow tract obstruction.2018

    • Author(s)
      Sakaguchi Y, Ozaki K, Takano T, Namba H, Tanaka K, Yanagawa T, Ozawa T, Minamino T.
    • Journal Title

      J Cardiol Cases.

      Volume: 18 Pages: 60-64.

    • DOI

      . doi: 10.1016/j.jccase.2018.04.010.

    • Peer Reviewed / Open Access
  • [Journal Article] Burden of cardiovascular disease in Japanese cancer patients and survivors: a single cancer-center study in Niigata City.2018

    • Author(s)
      Okura Y, Takayama T, Ozaki K, Tanaka H, Seki H, Takenouchi T, Sato N, Minamino T.
    • Journal Title

      Int J Clin Oncol.

      Volume: 印刷中 Pages: 印刷中

    • DOI

      doi: 10.1007/s10147-018-1341-0.

    • Peer Reviewed / Open Access
  • [Journal Article] Aortic carboxypeptidase-Like protein, a WNT ligand, exacerbates nonalcoholic steatohepatitis.2018

    • Author(s)
      Teratani T, Tomita K, Suzuki T, Furuhashi H, Irie R, Nishikawa M, Yamamoto J, Hibi T, Miura S, Minamino T, Oike Y, Hokari R, and Kanai T.
    • Journal Title

      J Clin Invest.

      Volume: 128 Pages: 1581-1596.

    • DOI

      DOI: 10.1172/JCI92863

    • Peer Reviewed / Open Access
  • [Journal Article] Effects of direct oral anticoagulants at the peak phase, the trough phase, and after vascular injury.2018

    • Author(s)
      Otuki S, Izumi D, Suda M, Sato A, Hasegawa Y, Yagihara N, Iijima K, Chinushi M, Fuse I, Minamino T
    • Journal Title

      J Am Coll Cardiol.

      Volume: 71 Pages: 102-104.

    • DOI

      DOI: 10.1016/j.jacc.2017.10.076

    • Peer Reviewed / Open Access
  • [Journal Article] Hematopoietic insults damage bone marrow niche by activating p53 in vascular endothelial cells.2018

    • Author(s)
      Si S, Nakajima-Takagi Y, Iga T, Tsuji M, Hou L, Oshima M, Koide S, Saraya A, Yamazaki S, Takubo K, Kubota Y, Minamino T※, Iwama A.
    • Journal Title

      Exp Hematol.

      Volume: 63 Pages: 41-51.

    • DOI

      DOI: 10.1016/j.exphem.2018.04.006

    • Peer Reviewed / Open Access
  • [Journal Article] Boysenberry polyphenol inhibits endothelial dysfunction and improves vascular health.2018

    • Author(s)
      Furuuchi R, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Suda M, Katsuumi G, Wakasugi T, Nakao M, Minamino T
    • Journal Title

      PLoS One.

      Volume: 13 Pages: e0202051.

    • DOI

      DOI: 10.1371/journal.pone.0202051

    • Peer Reviewed / Open Access
  • [Journal Article] Bidirectional shunt trajectory in ventricular septal defect with Eisenmenger's syndrome.2018

    • Author(s)
      Kayamori H, Kashimura T, Horii Y, Kanazawa T, Fujita T, Kubota N, Ikami Y, Takano T, Okubo T, Hoyano M, Yanagawa T, Ozawa T, Ozaki K, Minamino T.
    • Journal Title

      Circ J.

      Volume: 82 Pages: 2925-2926.

    • DOI

      DOI: 10.1253/circj.CJ-18-0332

    • Peer Reviewed / Open Access
  • [Journal Article] Efficacy of corticosteroid treatment for refractory multivessel vasospastic coronary angina with hypereosinophilia.2018

    • Author(s)
      Takano T, Ozaki K, Tanaka K, Yanagawa T, Ozawa T, Minamino T.
    • Journal Title

      Intern Med.

      Volume: 57 Pages: 3111-3115,

    • DOI

      DOI: 10.2169/internalmedicine.0886-18

    • Peer Reviewed / Open Access
  • [Journal Article] Prognosis of cancer patients with aortic stenosis under optimal cancer therapies and conservative cardiac treatments.2018

    • Author(s)
      Okura Y, Ishigaki S, Sakakibara S, Yumoto C, Hashitate M, Sekine C, Fujita T, Takayama T, Ozaki K, Sato N, Minamino T.
    • Journal Title

      Int Heart J.

      Volume: 59 Pages: 750-758.

    • DOI

      doi: 10.1536/ihj.17-320.

    • Peer Reviewed / Open Access
  • [Journal Article] Amlodipine inhibits vascular cell senescence and protects against atherogenesis through the mechanism independent of calcium channel blockade.2018

    • Author(s)
      Kayamori H, Shimizu I, Yoshida Y, Hayashi Y, Suda M, Ikegami R, Katsuumi G, Wakasugi T, Minamino T
    • Journal Title

      Int Heart J.

      Volume: 59 Pages: 607-613.

    • DOI

      DOI: 10.1536/ihj.17-265

    • Peer Reviewed / Open Access
  • [Journal Article] Catecholamine-induced senescence of endothelial cells and bone marrow cells promotes cardiac dysfunction in mice.2018

    • Author(s)
      Katsuumi G, Shimizu I, Yoshida Y, Hayashi Y, Ikegami R, Suda M, Wakasugi T, Nakao M, Minamino T
    • Journal Title

      Int Heart J.

      Volume: 59 Pages: 837-844.

    • DOI

      DOI: 10.1536/ihj.17-313

    • Peer Reviewed / Open Access
  • [Journal Article] Percutaneous Coronary intervention for a patient with left main coronary compression syndrome.2018

    • Author(s)
      Ikegami R, Ozaki K, Ozawa T, Hirono S, Ito M, Minamino T.
    • Journal Title

      Intern Med.

      Volume: 57 Pages: 1421-1424.

    • DOI

      DOI: 10.2169/internalmedicine.9534-17

    • Peer Reviewed / Open Access
  • [Journal Article] Aortic regurgitation presenting with recurrent detachment of a prosthetic valve, as the first presenting symptom of cardiovascular behcet's disease.2018

    • Author(s)
      Takayama T, Ozawa T, Sanada A, Watanabe T, Ito M, Hirono S, Aizawa Y, Minamino T.
    • Journal Title

      Intern Med.

      Volume: 57 Pages: 823-827.

    • DOI

      DOI: 10.2169/internalmedicine.9603-17

    • Peer Reviewed / Open Access
  • [Journal Article] Dual antiplatelet therapy guided by CYP2C19 polymorphisms after implantation of second-generation drug-eluting stents for management of acute coronary syndrome.2018

    • Author(s)
      Ozawa T, Suda M, Ikegami R, Takano T, Wakasugi T, Yanagawa T, Tanaka K, Ozaki K, Hirono S, Minamino T.
    • Journal Title

      Int Heart J.

      Volume: 59 Pages: 21-26.

    • DOI

      DOI: 10.1536/ihj.17-005

    • Peer Reviewed / Open Access
  • [Journal Article] Atrial fibrillation in patients with end-stage kidney disease on dialysis.2018

    • Author(s)
      Watanabe H, Minamino T.
    • Journal Title

      Intern Med.

      Volume: 57 Pages: 2285-2286.

    • DOI

      DOI: 10.2169/internalmedicine.0735-17

    • Peer Reviewed / Open Access
  • [Journal Article] Vascular senescence in cardiovascular and metabolic diseases.2018

    • Author(s)
      Katsuumi G, Shimizu I, Yoshida Y, Minamino T
    • Journal Title

      Front Cardiovasc Med.

      Volume: 5 Pages: 18.

    • DOI

      doi: 10.3389/fcvm.2018.00018.

    • Peer Reviewed / Open Access
  • [Presentation] Targeting Cardiovascular Senescence through Senescence-associated Glycoprotein.2019

    • Author(s)
      Minamino T.
    • Organizer
      The 14th Annual Winter Research Meeting on Translational Heart Failure Research,
    • Int'l Joint Research / Invited
  • [Presentation] Targeting Cellular Aging for Cardio-metabolic Disease.2019

    • Author(s)
      Minamino T.
    • Organizer
      The 3rd Annual 2019 International Hawaii Cardiovascular Symposium,
    • Int'l Joint Research / Invited
  • [Presentation] Targeting cellular aging for the treatment of cardiovascular diseases.2018

    • Author(s)
      Minamino T.
    • Organizer
      “Myocardial aging and cardiometabolic disorders”
    • Int'l Joint Research / Invited
  • [Presentation] Role of Cellular Aging in Cardio-metabolic Disease.2018

    • Author(s)
      Minamino T.
    • Organizer
      24th IUBMB Congress & 15th FAOBMB Congress
    • Int'l Joint Research / Invited
  • [Presentation] Role of Cellular Aging in Cardio-metabolic Disease.2018

    • Author(s)
      Minamino T.
    • Organizer
      The 18th World Congress of Basic and Clinical Pharmacology (WCP2018) Symposium
    • Int'l Joint Research / Invited
  • [Presentation] Targeting cellular aging for the treatment of cardiovascular diseases.2018

    • Author(s)
      Minamino T.
    • Organizer
      BCVS 2018 Scientific Sessions Mitochondrion and Heart Failure,
    • Int'l Joint Research / Invited
  • [Presentation] White and brown adipose tissue as a therapeutic target for cardiovascular diseases.2018

    • Author(s)
      Minamino T.
    • Organizer
      ESC 2018
    • Int'l Joint Research / Invited
  • [Presentation] Targeting cellular aging for the treatment of cardio-metabolic disease.2018

    • Author(s)
      Minamino T.
    • Organizer
      9TH ANNUAL ALLIANCE FOR HEALTHY AGING CONFERENCE,
    • Int'l Joint Research / Invited
  • [Presentation] Targeting metabolites for HF treatment.2018

    • Author(s)
      Minamino T.
    • Organizer
      The 62nd Annual Scientific Meeting of the Korean Society of Cardiology,
    • Int'l Joint Research / Invited
  • [Presentation] Novel Aspects of Direct Oral Anticoagulants.2018

    • Author(s)
      Minamino T.
    • Organizer
      American Heart Association,
    • Int'l Joint Research / Invited
  • [Presentation] 循環器疾患における糖尿病のトータルマネジメントを考える-基礎から臨床へ-2018

    • Author(s)
      Minamino T.
    • Organizer
      第248回日本循環器学会 関東甲信越地方会
    • Invited
  • [Presentation] 老化シグナルと心血管代謝ネットワーク2018

    • Author(s)
      Minamino T.
    • Organizer
      第60回日本老年医学会学術集会
    • Invited
  • [Presentation] 心不全の代謝異常と分子病態からみた心臓リハビリテーションの展望2018

    • Author(s)
      Minamino T.
    • Organizer
      第24回日本心臓リハビリテーション学会学術集会
    • Invited
  • [Presentation] 老化からみた心臓リハビリテーションの展望2018

    • Author(s)
      Minamino T.
    • Organizer
      第24回日本心臓リハビリテーション学会学術集会
    • Invited
  • [Presentation] 老化制御研究からみた健康寿命延伸の展望2018

    • Author(s)
      Minamino T.
    • Organizer
      第59回日本人間ドック学会
    • Invited
  • [Presentation] 心不全発症メカニズムから見た高血圧治療戦略2018

    • Author(s)
      Minamino T.
    • Organizer
      第41回日本高血圧学会総会
    • Invited
  • [Presentation] Senolysis as a novel therapeutic strategy for cardio-metabolic disease2018

    • Author(s)
      Minamino T.
    • Organizer
      第83回日本循環器学会学術総会
    • Invited
  • [Book] 近未来の心不全治療薬の展望2019

    • Author(s)
      南野 徹
    • Total Pages
      377
    • Publisher
      心臓
  • [Book] 下壁由来の心室期外収縮が心室細動のトリガーと考えられたBrugada症候群の1例2018

    • Author(s)
      久保田 直樹, 長谷川 祐紀, 佐藤 光希, 松尾 聖, 八木原 伸江, 飯嶋 賢一, 和泉 大輔, 南野 徹
    • Total Pages
      75-82
    • Publisher
      心臓
  • [Book] Cabrol graftと両側冠動脈の吻合部狭窄に対して待機的PCIを施行したMarfan症候群の一例2018

    • Author(s)
      山口祐美、尾崎和幸、高野俊樹、高山亜美、保屋野真、栁川貴央、岡本竹司、小澤拓也、柏村 健、名村 理、南野 徹
    • Total Pages
      902-907.
    • Publisher
      心臓
  • [Book] 重症大動脈弁狭窄症を合併し心破裂を生じた急性心筋梗塞の一例2018

    • Author(s)
      松尾佑治、尾崎和幸、高野俊樹、渡邊 達、保屋野真、柳川貴央、小澤拓也、柏村 健、南野 徹
    • Total Pages
      1041-1046.
    • Publisher
      心臓
  • [Book] QT短縮症候群の病態と治療(解説)2018

    • Author(s)
      八木原伸江、渡部裕、南野徹
    • Total Pages
      713-720.
    • Publisher
      科学評論社
  • [Book] 脂肪の量と質を制御するー老化による制御2018

    • Author(s)
      池上龍太郎、清水逸平、吉田陽子、南野 徹
    • Total Pages
      2739-2743.
    • Publisher
      実験医学
  • [Book] 心血管代謝疾患におけるSASP因子の役割2018

    • Author(s)
      南野 徹
    • Total Pages
      69-73
    • Publisher
      北隆館
  • [Book] 血管疾患のアンチエイジング治療2018

    • Author(s)
      仲尾政晃、清水逸平、南野 徹
    • Total Pages
      873-877
    • Publisher
      心臓
  • [Book] アンチエイジング医学2018

    • Author(s)
      萱森裕美、南野 徹
    • Total Pages
      494-499
    • Publisher
      概日リズムと循環器疾患
  • [Book] 細胞老化を標的とした循環代謝制御2018

    • Author(s)
      南野 徹
    • Total Pages
      1-7.
    • Publisher
      血管
  • [Book] 老化からみた生活習慣病診療の展望2018

    • Author(s)
      南野 徹
    • Total Pages
      161-166
    • Publisher
      新潟医学会雑誌
  • [Book] 概日リズムと生活習慣病の観点からみた睡眠薬の適正使用2018

    • Author(s)
      須田将吉、清水逸平、南野 徹
    • Total Pages
      819-823,
    • Publisher
      ANTI-AGING MEDICINE
  • [Book] 動脈硬化と老化2018

    • Author(s)
      池上 龍太郎、南野 徹
    • Total Pages
      61-65
    • Publisher
      科学評論社
  • [Remarks] 新潟大学大学院医歯学総合研究科 循環器内科

    • URL

      http://www.med.niigata-u.ac.jp/car/

  • [Patent(Industrial Property Rights)] 特願2018

    • Inventor(s)
      南野 徹,飯島 賢一
    • Industrial Property Rights Holder
      南野 徹,飯島 賢一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2018-218050

URL: 

Published: 2019-12-27  

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