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The elucidation of the role of chronic inflammation in heart failure.

Research Project

Project/Area Number 24390064
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field General pharmacology
Research InstitutionShitennoji University (2014)
Osaka City University (2012-2013)

Principal Investigator

IWAO Hiroshi  四天王寺大学, 教育学部, 教授 (00137192)

Co-Investigator(Kenkyū-buntansha) IZUMI Yasukatsu  大阪市立大学, 大学院医学研究科, 准教授 (10347495)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2012: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
Keywordsマクロファージ / エクソソーム / 心リモデリング / 内皮細胞 / HIF-1alpha / HSP70
Outline of Final Research Achievements

Hypertension is one of the most important cardiovascular risk factors, and results in macrophage infiltration into the tissues. Here, we investigated the role of exosome, one of extracellular vesicles, in the inflammatory pathways of endothelial cells (ECs) under hypertensive conditions.
Exosomes were purified by ultracentrifugation. The exosomes isolated from angiotensin II-infused rat serum abundantly contained macrophage marker proteins, CD68 and CD45. Moreover, exosomes from hypertensive rat serum immediately activated intracellular signals such as c-jun N-terminal kinase and p38 mitogen-activated protein kinase, and upregulated the expression of intracellular adhesion molecule-1 in ECs. Interestingly, exosomes from THP-1-derived macrophages stimulated by Angiotensin II also activated these signaling pathways in ECs.
These results suggest that macrophage-derived exosomes under hypertensive conditions activate the inflammatory pathway in ECs, leading to cardiovascular remodeling.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (44 results)

All 2015 2014 2013 2012

All Journal Article (17 results) (of which Peer Reviewed: 16 results,  Open Access: 7 results,  Acknowledgement Compliant: 1 results) Presentation (27 results) (of which Invited: 1 results)

  • [Journal Article] Myeloid HIF-1 attenuates the progression of renal fibrosis in murine obstructive nephropathy.2015

    • Author(s)
      Tateishi,Y, Osada-Oka M, Tanaka M, Shiota M, Izumi Y, Ishimura E, Motoyama K, Inaba M, Miura, K.
    • Journal Title

      J Pharmacol Sci

      Volume: 127 Issue: 2 Pages: 181-189

    • DOI

      10.1016/j.jphs.2014.12.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Percutaneous Carbon Dioxide Treatment using a Gas Mist Generator Enhances the Collateral Blood Flow in the Ischemic Hindlimb2015

    • Author(s)
      Izumi, Y
    • Journal Title

      Journal of Atherosclerosis and Thrombosis

      Volume: 22 Issue: 1 Pages: 38-51

    • DOI

      10.5551/jat.23770

    • NAID

      130004677973

    • ISSN
      1340-3478, 1880-3873
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Percutaneous carbon dioxide mist treatment has protective effects in experimental myocardial infarction.2015

    • Author(s)
      Yamaguchi T, Yamazaki T, Nakamura Y, Shiota M, Shimada K, Miura K, Iwao H, Yoshiyama M, Izumi Y.
    • Journal Title

      J Pharmacol Sci

      Volume: 印刷中

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Repeated remote ischemic conditioning attenuates left ventricular remodeling via exosome-mediated intercellular communication on chronic heart failure after myocardial infarction2014

    • Author(s)
      Yamaguchi, T
    • Journal Title

      Int J Cardiol

      Volume: 30 Pages: 239-246

    • DOI

      10.1016/j.ijcard.2014.10.144

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Noninvasive Metabolic Syndrome Model Using an Extremely Small Minipig, the Microminipig2014

    • Author(s)
      Yamaguchi, T
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 126 Issue: 2 Pages: 168-171

    • DOI

      10.1254/jphs.14171SC

    • NAID

      130004690915

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of neutralizing rat monoclonal antibodies for fibroblast growth factor-22014

    • Author(s)
      Tanaka M, Yamaguchi M, Shiota M, Kawamoto Y, Takahashi K, Inagaki A, Osada-Oka M, Harada A, Wanibuchi H, Izumi Y, Miura K, Iwao H, Ohkawa Y.
    • Journal Title

      Monoclon Antib Immunodiagn Immunother

      Volume: 33 Issue: 4 Pages: 261-269

    • DOI

      10.1089/mab.2013.0085

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Hsc70 contributes to cancer cell survival by preventing Rab1A degradation under stress conditions.2014

    • Author(s)
      Tanaka M, Mun S, Harada A, Ohkawa Y, Inagaki A, Sano S, Takahashi K, Izumi Y, Osada-Oka M, Wanibuchi H, Yamagata M, Yukimura T, Miura K, Shiota M, Iwao H.
    • Journal Title

      PLoS One

      Volume: 9 Issue: 5 Pages: e96785-e96785

    • DOI

      10.1371/journal.pone.0096785

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lipid synthesis is promoted by hypoxic adipocyte-derived exosomes in 3T3-L1cells2014

    • Author(s)
      Sano S, Izumi Y, Yamaguchi T, Yamazaki T, Tanaka M, Shiota M, Osada-Oka M, Nakamura Y, Wei M, Wanibuchi H, Iwao H, Yoshiyama M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 445 Issue: 2 Pages: 327-33

    • DOI

      10.1016/j.bbrc.2014.01.183

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Potential of Vasopressin-Receptor Antagonists in Heart Failure2014

    • Author(s)
      Izumi Y, Miura K, Iwao H.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 124 Issue: 1 Pages: 1-6

    • DOI

      10.1254/jphs.13R13CP

    • NAID

      130003382634

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Establishment of a 5-fluorouracil-resistant triple-negative breast cancer cell line2013

    • Author(s)
      Takahashi K, Tanaka M, Inagaki A, Wanibuchi H, Izumi Y, Miura K, Nagayama K, Shiota M, Iwao H.
    • Journal Title

      Int J Oncol.

      Volume: 43 Issue: 6 Pages: 1985-91

    • DOI

      10.3892/ijo.2013.2135

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tolvaptan Attenuates Left Ventricular Fibrosis After Acute Myocardial Infarction in Rats2013

    • Author(s)
      Yamazaki T, Nakamura Y, Shiota M, Osada-Oka M, Fujiki H, Hanatani A, Shimada K, Miura K, Yoshiyama M, Iwao H, Izumi Y.
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 123 Issue: 1 Pages: 58-66

    • DOI

      10.1254/jphs.13086FP

    • NAID

      10031202963

    • ISSN
      1347-8613, 1347-8648
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Drug-Induced Takotsubo Cardiomyopathy.2013

    • Author(s)
      Izumi Y.
    • Journal Title

      Heart Failure Clinics

      Volume: 9 Issue: 2 Pages: 225-231

    • DOI

      10.1016/j.hfc.2012.12.004

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Pravastatin-induced proangiogenic effects depend upon extracellular FGF-2.2012

    • Author(s)
      Shiota M, Hikita Y, Kawamoto Y, Kusakabe H, Tanaka M, Izumi Y, Nakao T, Miura K, Funae Y Iwao H
    • Journal Title

      J Cell Mol Med.

      Volume: 16 Pages: 2001-2009

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Angiotensin AT1 receptor blockers suppress oxidized low-density lipoprotein-derived formation of foam cells.2012

    • Author(s)
      Osada-Oka M, Kita H, Yagi S, Sato T, Izumi Y, Iwao H
    • Journal Title

      Eur J Pharmacol.

      Volume: 679 Issue: 1-3 Pages: 9-15

    • DOI

      10.1016/j.ejphar.2011.12.044

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel device that produces carbon dioxide mist for myocardial infarction treatment in rats.2012

    • Author(s)
      Yamazaki T, Izumi Y, Nakamura Y, Hanatani A, Shimada K, Muro T, Shiota M, Iwao H, Yoshiyama M
    • Journal Title

      Circ J.

      Volume: 76 Pages: 1203-1212

    • NAID

      10030132718

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Red ginseng inhibits scratching behavior associated with atopic dermatitis in experimental animal models.2012

    • Author(s)
      Samukawa K, Izumi Y Shiota M, Nakao T, Osada-Oka M, Miura K, Iwao H.
    • Journal Title

      J Pharmacol Sci.

      Volume: 118 Pages: 391-400

    • NAID

      10030455761

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Tolvaptan improves left ventricular dysfunction after myocardial infarction in rats.2012

    • Author(s)
      Yamazaki T, Izumi y Nakamura Y, Yamashita N, Fujiki H, Osada-Oka M, Shiota M, Hanatani A, Shimada K, Iwao H, Yoshiyama M.
    • Journal Title

      Circ Heart Fail.

      Volume: 5 Issue: 6 Pages: 794-802

    • DOI

      10.1161/circheartfailure.112.968750

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] レニン・アンジオテンシン系研究と心血管病2015

    • Author(s)
      岩尾 洋
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] エクソソームを介した心血管疾患制御2015

    • Author(s)
      泉 康雄、山口 雄大、岡 真優子、塩田 正之、田中 昌子、三浦 克之、岩尾 洋
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] Stromal cell-derived factor 2はoxaliplatin耐性に寄与する2015

    • Author(s)
      高橋 克之、田中 昌子、塩田 正之、泉 康雄、三浦 克之、岩尾 洋
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 四肢の虚血コンディショニングはエクソソームを介した情報伝達によって心リモデリングを抑制する2015

    • Author(s)
      山口 雄大、葭山 稔、塩田 正之、田中 昌子、三浦 克之、岩尾 洋、泉 康雄
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 低血清・低酸素耐性膵癌細胞におけるゲムシタビン感受性の評価2015

    • Author(s)
      市坪 大将、田中 昌子、高橋 克之、泉 康雄、塩田 正之、岩尾 洋、三浦 克之
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 紅蔘エキスによる好塩基球のp70S6キナーゼ阻害と抗アレルギー作用2015

    • Author(s)
      岡 真優子、平井 沙也花、南山 幸子、寒川 慶一、岩尾 洋、泉 康雄
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場(愛知県・名古屋市)
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] 一過性の遠隔部虚血コンディショニングはエクソソームを介して心保護作用を発揮する2014

    • Author(s)
      泉 康雄、山口 雄大、岡 真優子、田中 昌子、塩田 正之、葭山 稔、三浦 克之、岩尾 洋
    • Organizer
      第24回日本循環薬理学会
    • Place of Presentation
      山形テルサ(山形県・山形市)
    • Year and Date
      2014-12-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] 膵癌細胞における低血清・酸素耐性株の樹立と 膵癌細胞における低血清・酸素耐性株の樹立とGemcitabone感受性の評価2014

    • Author(s)
      市坪 大将、田中 昌子、髙橋 克之、泉 康雄、塩田正之、三浦克之、岩尾 洋
    • Organizer
      第126回日本薬理学会近畿部会
    • Place of Presentation
      和歌山県JAビル(和歌山県・和歌山市)
    • Year and Date
      2014-10-24
    • Related Report
      2014 Annual Research Report
  • [Presentation] 超小型ミニブタを用いたメタボリック症候群モデルの作製2014

    • Author(s)
      泉 康雄、中村 泰浩、山崎 貴紀、島田 健永、葭山 稔、岩尾 洋
    • Organizer
      第37回日本高血圧学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-10-17 – 2014-10-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] 活性化マクロファージ由来エキソソームと血管内皮細胞障害2014

    • Author(s)
      岡 真優子、塩田正之、田中昌子、泉 康雄、岩尾 洋
    • Organizer
      第87回 日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府・京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Exosome-mediated intercellular communication by repetitive remote ischemic conditioning reduces left ventricular remodeling on chronic heart failure.2014

    • Author(s)
      Takehiro Yamaguchi, Yasukatsu Izumi, Takanori Yamazaki, Yasuhiro Nakamura, Soichi Sano, Akihisa Hanatani, Kenei Shimada, Hiroshi Iwao, Minoru Yoshiyama
    • Organizer
      European Society of Cardiology Scientific Session 2014
    • Place of Presentation
      Barcelona Convention Centre(バルセロナ・スペイン)
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Repetitive treatment of percutaneous carbon dioxide mist prevents high fat diet-induced arteriosclerosis in extremely small size minipig.2014

    • Author(s)
      Yasukatsu Izumi, Takehiro Yamaguchi, Hiroaki Kawaguchi, Masashi Tawa, Takanori Yamazaki, Masayuki Shiota, Akihide Tanimoto, Tomio Okamura, Minoru Yoshiyama, Hiroshi Iwao
    • Organizer
      European Society of Cardiology Scientific Session 2014
    • Place of Presentation
      Barcelona Convention Centre(バルセロナ・スペイン)
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Macrophage-derived exosomes damage endothelial cells in experimental hypertensive models.2014

    • Author(s)
      Yasukatsu Izumi, Takehiro Yamaguchi, Mayuko Osada-Oka, Masayuki Shiota, Masako Tanaka, Soichi Sano, Minoru Yoshiyama, Hiroshi Iwao
    • Organizer
      European Society of Cardiology Scientific Session 2014
    • Place of Presentation
      Barcelona Convention Centre(バルセロナ・スペイン)
    • Year and Date
      2014-08-30 – 2014-09-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 慢性心不全に対するremote ischemic conditioning効果2014

    • Author(s)
      泉 康雄、山口 雄大、岡 真優子、塩田 正之、田中 昌子、葭山 稔、三浦 克之、岩尾 洋
    • Organizer
      第125回日本薬理学会近畿部会
    • Place of Presentation
      岡山コンベンションセンター(岡山県・岡山市)
    • Year and Date
      2014-06-20
    • Related Report
      2014 Annual Research Report
  • [Presentation] The role of macrophage-derived exosomes in hypertension.2014

    • Author(s)
      Takehiro Yamaguchi, Hiroshi Iwao, Mayuko Osada-Oka, Masayuki Shiota, Masako Tanaka, Katsuyuki Miura, Minoru Yoshiyama, Yasukatsu Izumi
    • Organizer
      European Society of Hypertension/International Society of Hypertension 2014
    • Place of Presentation
      Megaron Athens International Cnferebce Centre(アテネ・ギリシャ)
    • Year and Date
      2014-06-13 – 2014-06-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] A nitric oxide synthase inhibitor accelerates high fat diet-induced arteriosclerosis in extremely small size minipig, Microminipig.2014

    • Author(s)
      Yasukatsu Izumi, TakehiroYamaguchi, Takanori Yamazaki, Hiroaki Kawaguchi, Masashi Tawa, Masayuki Shiota, Akihide Tanimoto, Tomio Okamura, Minoru Yoshiyama, Hiroshi Iwao
    • Organizer
      第18回国際血管生物学会
    • Place of Presentation
      都メッセ京都(京都府・京都市)
    • Year and Date
      2014-04-14 – 2014-04-17
    • Related Report
      2014 Annual Research Report
  • [Presentation] 慢性心不全に対する一過性四肢虚血コンディショニング効果2014

    • Author(s)
      泉 康雄、山口 雄大、山崎 貴紀、中村 泰浩、岡 真優子、塩田 正之、葭山 稔、岩尾 洋
    • Organizer
      第43回 日本心脈管作動物質学会
    • Place of Presentation
      神戸国際会議場(兵庫県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] The establishment of a noninvasive metabolic syndrome model using an extremely small size minipig, Microminipig2014

    • Author(s)
      泉 康雄、山口 雄大、川口 博明、田和 正志、塩田 正之、岡 真優子、谷本 昭英、岡村 富夫、三浦 克之、岩尾 洋
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Endothelial cell dysfunction via hypoxia macrophage-derived exosomes2014

    • Author(s)
      岡 真優子、西山 方規、泉 康雄、塩田 正之、田中 昌子、三浦 克之、岩尾 洋
    • Organizer
      第87回日本薬理学会年会
    • Place of Presentation
      仙台国際センター(宮城県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 心血管病克服に向けた新たなパラダイム2013

    • Author(s)
      岩尾洋
    • Organizer
      第42回 日本心脈管作動物質学会
    • Place of Presentation
      奈良(招待講演)
    • Year and Date
      2013-02-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] ラット心筋梗塞急性期および慢性期に対するバソプレシンV_2受容体拮抗薬の有効性2013

    • Author(s)
      泉康雄
    • Organizer
      第42回 日本心脈管作動物質学会
    • Place of Presentation
      奈良
    • Year and Date
      2013-02-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] アンジオテンシンIIによるエクソソームへの影響2013

    • Author(s)
      西山方規
    • Organizer
      第42回 日本心脈管作動物質学会
    • Place of Presentation
      奈良
    • Year and Date
      2013-02-08
    • Related Report
      2012 Annual Research Report
  • [Presentation] 超小型ミニブタを用いた、非侵襲的メタボリック症候群モデルの作製2013

    • Author(s)
      泉 康雄、川口 博明、田和 正志、山崎 貴紀、山口 雄大、岡 真優子、塩田 正之、葭山 稔、谷本 昭英、岡村 富夫、岩尾 洋
    • Organizer
      第49回高血圧関連疾患モデル学会
    • Place of Presentation
      日本大学会館(東京都)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高血圧におけるエキソソームの役割2013

    • Author(s)
      泉 康雄、岡 真優子、塩田 正之、岩尾 洋
    • Organizer
      第36回日本高血圧学会総会
    • Place of Presentation
      大阪国際会議場(大阪府)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Beneficial effects of repeated remote ischemic conditioning on chronic heart failure at chronic phase after myocardial infarction2013

    • Author(s)
      Takehiro Yamaguchi, Yasukatsu Izumi, Takanori Yamazaki, Yasuhiro Nakamura, Soichi Sano, Akihisa Hanatani, Kenei Shimada, Hiroshi Iwao, Minoru Yoshiyama
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      ダラスコンベンションセンター(米国)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高血圧モデルにおけるマクロファージ由来エキソソームの内皮への影響2013

    • Author(s)
      泉 康雄、岡 真優子、西山 方規、田中 昌子、山口 雄大、塩田 正之、岩尾 洋
    • Organizer
      第17回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      千里ライフサイエンスセンター(大阪府)
    • Related Report
      2013 Annual Research Report
  • [Presentation] エクソソームを介した高血圧症による血管機能障害2012

    • Author(s)
      岡真優子
    • Organizer
      第122回 日本薬理学会近畿部会
    • Place of Presentation
      大阪
    • Year and Date
      2012-11-16
    • Related Report
      2012 Annual Research Report

URL: 

Published: 2012-04-24   Modified: 2019-07-29  

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