The role of exosome on the onset and development of arteriosclerosis

• Project/Area Number: 26460344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka City University
• Principal Investigator: Izumi Yasukatsu 大阪市立大学, 大学院医学研究科, 非常勤講師 (10347495)
• Co-Investigator(Renkei-kenkyūsha): SHIOTA Masayuki 大阪市立大学, 大学院医学研究科, 講師 (30381990)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: エキソソーム / 動脈硬化 / 内皮障害

Outline of Final Research Achievements

Metabolic syndrome (MetS) induces serious complications. We succeeded a noninvasive MetS model using an extremely small minipig. The protein level of serum exosomes in this model was increased, compared with that in normal diet group. Unfortunately, we viewed harshly the continuation of the analysis in this model. Therefore, we performed the analysis using a mouse model.
The deficient mice with neither endothelial nitric oxide synthase nor apolipoprotein E were used. The mice acutually expressed both hypertension and dyslipidemia by normal diet. We established the extraction and purification method from mouse serum exosomes.

Research Products

• [Journal Article] Macrophage-derived exosomes induce inflammatory factors in endothelial cells under hypertensive conditions. (2017)
  • Author(s): Osada-Oka M, Shiota M, Izumi Y, Nishiyama M, Tanaka M, Yamaguchi T, Sakurai E, Miura K, Iwao H.
  • Journal Title: Hypertens Res Volume: 40 Issue: 4 Pages: 353-360
  • DOI: 10.1038/hr.2016.163
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Protection of stromal cell-derived factor 2 by heat shock protein 72 prevents oxaliplatin-induced cell death in oxaliplatin-resistant human gastric cancer cells. (2016)
  • Author(s): Takahashi K, Tanaka M, Yashiro M, Matsumoto M, Ohtsuka A, Nakayama KI, Izumi Y, Nagayama K, Miura K, Iwao H, Shiota M.
  • Journal Title: Cancer Lett. Volume: 378 Issue: 1 Pages: 8-15
  • DOI: 10.1016/j.canlet.2016.05.002
  • Peer Reviewed
• [Journal Article] Four cases of investigational therapy with interleukin-11 against acute myocardial infarction. (2016)
  • Author(s): Nakagawa, M., Owada Y., Izumi, Y., Nonin, S., Sugioka, K., Nakatani, D., Iwata, S., Mizutani, K., Nishimura, S., It, A., Fujita, S., Daimon, T., Sawa, Y., Asakura, M., Maeda, M., Fujio, Y., Yoshiyama, M.
  • Journal Title: Heart and Vessels Volume: 31 Issue: 9 Pages: 1574-1578
  • DOI: 10.1007/s00380-015-0788-4
  • Peer Reviewed
• [Journal Article] A New Screen for Tuberculosis Drug Candidates Utilizing a Luciferase-Expressing Recombinant Mycobacterium bovis Bacillus Calmette-Guéren. (2015)
  • Author(s): 2)Ozeki Y, Igarashi M, Doe M, Tamaru A, Kinoshita N, Ogura Y, Iwamoto T, Sawa R, Umekita M, Enany S, Nishiuchi Y, Osada-Oka M, Hayashi T, Niki M, Tateishi Y, Hatano M, Matsumoto S.
  • Journal Title: PLoS One Volume: 10 Pages: 214-221
  • DOI: 10.1016/j.jprot.2016.01.008
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous carbon dioxide treatment using a gas mist generator attenuates the development of right ventricular dysfunction in monocrotaline-induced pulmonary hypertensive rats. (2015)
  • Author(s): Yamaguchi T, Izumi Y, Yamazaki T, Nakamura Y, Sano S, Shiota M, Miura K, Iwao H, Yoshiyama M.
  • Journal Title: Osaka City Med J Volume: 61 Pages: 31-41
  • NAID: 120006493314
  • Peer Reviewed
• [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
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Percutaneous Carbon Dioxide Treatment using a Gas Mist Generator Enhances the Collateral Blood Flow in the Ischemic Hindlimb (2015)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] A Noninvasive Metabolic Syndrome Model Using an Extremely Small Minipig, the Microminipig (2014)
  • 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
  • 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 infarction (2014)
  • Author(s): Yamaguchi, T
  • Journal Title: Int J Cardiol Volume: 30 Pages: 239-246
  • DOI: 10.1016/j.ijcard.2014.10.144
  • Peer Reviewed / Open Access
• [Journal Article] Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters (2014)
  • Author(s): Kato R
  • Journal Title: Am J Physiol Heart Circ Physiol Volume: 307 Issue: 11 Pages: H1626-H1633
  • DOI: 10.1152/ajpheart.00228.2014
  • Peer Reviewed
• [Presentation] 間歇的低酸素負荷にともなう心筋リモデリングに対する選択的Xa阻害薬rivaroxabanの影響 (2016)
  • Author(s): 坂井 伸次、冨士原 あゆみ、近藤 俊樹、藤井 健治、大丸 礎仁愛、今野 秀樹、加藤 隆児、 井尻 好雄、泉 康雄、葭山 稔、林 哲也
  • Organizer: 第37回日本臨床薬理学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県・米子市）
  • Year and Date: 2016-12-01
• [Presentation] 低酸素負荷に伴う心筋リモデリングに及ぼすVEGFR2チロシンキナーゼ阻害薬Sugen5416の影響 (2016)
  • Author(s): 橋本 知明、近藤 俊樹、冨士原 あゆみ、大丸 礎仁愛、藤井 健治、今野 秀樹、加藤 隆児、 井尻 好雄、泉 康雄、葭山 稔、林 哲也
  • Organizer: 第37回日本臨床薬理学会
  • Place of Presentation: 米子コンベンションセンター（鳥取県・米子市）
  • Year and Date: 2016-12-01
• [Presentation] 急性心筋梗塞に対するIL-11製剤オプレルベキンを用いた心筋保護治療 (2016)
  • Author(s): 野元 陽太、仲川 将志、泉 康雄、能仁 信一、坂本 勇也、水谷 一輝、白井 信幸、杉岡 憲一、 高木 雅彦、大和田 康子、前田 真貴子、中谷 大作、朝倉 正紀、藤尾 慈、葭山 稔
  • Organizer: 第64回日本心臓病学会学術集会
  • Place of Presentation: 東京国際フォーラム（東京都・千代田区）
  • Year and Date: 2016-09-23
• [Presentation] Macrophage-derived exosomes under hypertensive conditions cause inflammation in endothelial cells. (2016)
  • Author(s): Yasukatsu Izumi1, Takehiro Yamaguchi, Mayuko Osada-Oka, Masayuki Shiota, Masako Tanaka, Katsuyuki Miura, Shuhei Tomita, Hiroshi Iwao
  • Organizer: European Society of Cardiology Scientific Session 2016
  • Place of Presentation: ローマ（イタリア）
  • Year and Date: 2016-08-27
  • Int'l Joint Research
• [Presentation] Cardioprotective Effect of Linagliptin independently of Dipeptidyl Peptidase-4 in Rat Myocardial Infarction Model (2016)
  • Author(s): Takehiro Yamaguchi, Takanori Yamazaki, Yasuhiro Nakamura, Kenei Shimada, Minoru Yoshiyama, Yasukatsu Izumi.
  • Organizer: 第80回日本循環器学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2016-03-18
• [Presentation] 高血圧ラットにおける血中エキソソームの内皮細胞への役割 (2016)
  • Author(s): 泉 康雄、櫻井 絵未、岡 真優子、田中 昌子、塩田 正之、岩尾 洋、三浦 克之
  • Organizer: 第45回日本心脈管作動物質学会
  • Place of Presentation: ホテルサンルート徳島（徳島県・徳島市）
  • Year and Date: 2016-02-05
• [Presentation] DPP-4阻害薬のDPP-4非依存的な心保護作用 (2015)
  • Author(s): 泉 康雄、山口 雄大、渡邉 綾乃、田中 昌子、岡 真優子、塩田 正之、岩尾 洋、三浦 克之
  • Organizer: 第25回日本循環薬理学会
  • Place of Presentation: 東大寺ミュージアム（奈良県・奈良市）
  • Year and Date: 2015-12-04
• [Presentation] 高血圧ラットの血中エキソソームは内皮細胞の炎症を惹起する (2015)
  • Author(s): 櫻井 絵未、岡 真優子、田中 昌子、山口 雄大、塩田 正之、岩尾 洋、三浦 克之、泉 康雄
  • Organizer: 第128回日本薬理学会近畿部会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府・大阪市）
  • Year and Date: 2015-11-20
• [Presentation] 肺高血圧による右室モデリングに対する炭酸ガスミストの有効性 (2015)
  • Author(s): 泉 康雄、山崎 貴紀、中村 泰浩、岩尾 洋
  • Organizer: 第38回日本高血圧学会総会
  • Place of Presentation: ひめぎんホール（愛媛県・松山市）
  • Year and Date: 2015-10-09
• [Presentation] Percutaneous treatment of carbon dioxide mist attenuates the development of right ventricular dysfunction in monocrotaline-induced pulmonary hypertensive rats. (2015)
  • Author(s): Takehiro Yamaguchi, Yasukatsu Izumi, Takanori Yamazaki, Yasuhiro Nakamura, Kenei Shimada, Minoru Yoshiyama, Hiroshi Iwao.
  • Organizer: European Society of Cardiology Scientific Session 2015
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Cardioprotective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors independently of DPP-4. (2015)
  • Author(s): Takehiro Yamaguchi, Yasukatsu Izumi, Takanori Yamazaki, Yasuhiro Nakamura, Kenei Shimada, Minoru Yoshiyama, Hiroshi Iwao.
  • Organizer: European Society of Cardiology Scientific Session 2015
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Delayed overexpression of vascular endothelial growth factor in the right ventricular myocardium accelerates irreversible cardiac remodeling in pulmonary arterial hypertension. (2015)
  • Author(s): E Woo, S Hosako, J Kawakami, R Kato, Y Ijiri, T Yamaguchi, Y Izumi, M Yoshiyama, T katsumata, T Hayashi.
  • Organizer: European Society of Cardiology Scientific Session 2015
  • Place of Presentation: ロンドン（イギリス）
  • Year and Date: 2015-08-29
  • Int'l Joint Research
• [Presentation] Gp130サイトカインと心血管病 (2015)
  • Author(s): 藤尾慈、前田真貴子、朝倉正紀、中谷大作、泉康雄、葭山稔
  • Organizer: 第1回国際心血管薬物療法学会日本部会
  • Place of Presentation: 京都国際会館（京都府・京都市）
  • Year and Date: 2015-06-20
• [Presentation] DPP-4阻害薬LinagliptonのGLP-1非依存的心保護作用 (2015)
  • Author(s): 渡邉綾乃、山口 雄大、岡 真優子、田中 昌子、塩田 正之、岩尾 洋、三浦 克之、泉 康雄
  • Organizer: 第127回日本薬理学会近畿部会
  • Place of Presentation: 長良川国際会議場（岐阜県・岐阜市）
  • Year and Date: 2015-06-20
• [Presentation] ゲムシタビン耐性ヒト膵癌細胞株における生存因子の同定 (2015)
  • Author(s): 田中 昌子、高橋 克之、泉 康雄、三浦 克之、塩田 正之
  • Organizer: 第127回日本薬理学会近畿部会
  • Place of Presentation: 長良川国際会議場（岐阜県・岐阜市）
  • Year and Date: 2015-06-20
• [Presentation] Percutaneous Treatment of Carbon Dioxide Mist Attenuates the Right Ventricular Remodeling due to Monocrotaline-Induced Pulmonary Hypertension. (2015)
  • Author(s): Takehiro Yamaguchi, Yasukatsu Izumi, Takanori Yamazaki, Soichi Sano, Yasuhiro Nakamura, Kenei Shimada, Minoru Yoshiyama.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2015-04-24
• [Presentation] Serum Brain-Derived Neurotrophic Factor Level at Discharge Predicts the Prognosis in Patients with Heart Failure. (2015)
  • Author(s): Atsushi Shibata, Yasukatsu Izumi, Akihisa Hanatani, Ryoko Kitada, Shoichi Ehara, Masahiko Takagi, Takeshi Hozumi, Kenei Shimada, Minoru Yoshiyama
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2015-04-24
• [Presentation] Serum Irisin Level Increase in Short-Term Rehabilitation during Hospitalization Predicts the Prognosis in Patients with Heart Failure. (2015)
  • Author(s): Atsushi Shibata, Yasukatsu Izumi, Akihisa Hanatani, Ryoko Kitada, kenichi Sugioka, Shoichi Ehara, Masahiko Takagi, Takeshi Hozumi, Kenei Shimada, Minoru Yoshiyama.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2015-04-24
• [Presentation] Crosstalk between O-GlcNAcylation and Phosphorylation Regulates Autophagy in Diabetes Mellitus and OGT-Tg Mice Exposed to Intermittent Hypoxia. (2015)
  • Author(s): Atsuo Nomura, Ryuji Kato, Yoshio Ijiri, Takehiro Yamaguchi, Yasukatsu Izumi, Minoru Yoshiyama, Michio Asahi, Tetsuya Hayashi.
  • Organizer: 第79回日本循環器学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府・大阪市）
  • Year and Date: 2015-04-24
• [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
• [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
• [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
• [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
• [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 Center (バルセロナ・スペイン)
  • Year and Date: 2014-08-30 – 2014-09-03
• [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 Center (バルセロナ・スペイン)
  • Year and Date: 2014-08-30 – 2014-09-03
• [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
  • Place of Presentation: Megaron Athens International Conference Center (アテネ・ギリシャ）
  • Year and Date: 2014-06-13 – 2014-06-16
• [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