• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Elucidation of pathophysiology of aortic dissection and development of the preventive strategies by medical big data and novel model mice

Research Project

Project/Area Number 18K06686
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionThe University of Tokushima

Principal Investigator

ISHIZAWA Keisuke  徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60398013)

Co-Investigator(Kenkyū-buntansha) 今西 正樹  徳島大学, 病院, 助教 (00734344)
石澤 有紀  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (40610192)
座間味 義人  徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (70550250)
合田 光寛  徳島大学, 病院, 特任助教 (40585965)
武智 研志  徳島大学, 病院, 特任助教 (90793240)
中馬 真幸  旭川医科大学, 大学病院, 講師 (20819289)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords大動脈解離 / 大動脈瘤 / 医療ビッグデータ / 有害事象自発報告データベース / 血管内皮障害 / ERK5 / 大規模医療情報データベース / ドラッグリポジショニング / 内皮機能障害 / 動脈硬化 / 血管内皮 / ビッグデータ
Outline of Final Research Achievements

Aortic dissection is a condition in which the aortic wall is separated into two layers by the media to form a false lumen. Since it develops suddenly and progresses rapidly, rapid treatment is required. This feature of aortic dissection complicates clinical studies in humans. Therefore, it is difficult to establish a completely new treatment strategy. In addition, basic research such as elucidation of the pathophysiology and molecular mechanism of aortic dissection has not progressed sufficiently. In this research, we succeeded in extracting candidate drugs that are expected to prevent the onset of aortic dissection from approved drugs by a new research method using medical big data analysis. Furthermore, the efficacy of the candidate drugs was evaluated using a novel pharmacologically induced aortic dissection prone model mouse which we have established recently. As a result, we obtained the results that form the basis for proposing new preventive strategies.

Academic Significance and Societal Importance of the Research Achievements

大動脈解離の発症は加齢、高血圧、粥状動脈硬化、結合織疾患の既往等が危険因子となると言われており、近年罹患率が増加している。本疾患は突然死の原因にもなっており、急激な転帰をたどることから、発症を予防することが何より重要である。本研究では、医療ビッグデータを用いる新しい研究手法を導入することで、膨大な過去の症例を網羅的に探索し、効率的に予防候補薬剤を抽出した。さらに、新規薬剤誘発性大動脈解離易発症モデルマウスを用いることで、データベースから抽出した予防候補薬に併せ、食品由来成分のなかに解離発症に対する予防効果を示すものがあることを示した。これは、予防医学の観点からも社会的意義が大きい。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 8 results,  Open Access: 8 results) Presentation (13 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Preventive Effects of Quercetin against the Onset of Atherosclerosis-Related Acute Aortic Syndromes in Mice2020

    • Author(s)
      Kondo Masateru、Izawa-Ishizawa Yuki、Goda Mitsuhiro、Hosooka Mayuko、Kagimoto Yuu、Saito Naoko、Matsuoka Rie、Zamami Yoshito、Chuma Masayuki、Yagi Kenta、Takechi Kenshi、Tsuneyama Koichi、Ishizawa Keisuke
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 19 Pages: 7226-7226

    • DOI

      10.3390/ijms21197226

    • NAID

      120006891180

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fibroblast-specific ERK5 deficiency changes tumor vasculature and exacerbates tumor progression in a mouse model.2020

    • Author(s)
      Masaki Imanishi, Yusuke Yamakawa, Keijo Fukushima, Raiki Ikuto, Akiko Maegawa, Yuki Izawa-Ishizawa, Yuya Horinouchi, Masateru Kondo, Masatoshi Kishuku, Mitsuhiro Goda, Yoshito Zamami, Kenshi Takechi, Masayuki Chuma, Yasumasa Ikeda, Koichiro Tsuchiya, Hiromichi Fujino, Koichi Tsuneyama, Keisuke Ishizawa
    • Journal Title

      Naunyn-Schmiedeberg's Archives of Pharmacology

      Volume: - Issue: 7 Pages: 1239-1250

    • DOI

      10.1007/s00210-020-01859-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Rho-associated protein kinase and cyclophilin A are involved in inorganic phosphate-induced calcification signaling in vascular smooth muscle cells2020

    • Author(s)
      Tatsuya Tsuda, Masaki Imanishi, Mizuho Oogoshi, Yoshitaka Kihira, Yuya Horinouchi, Yoshito Zamami, Keisuke Ishizawa, Yasumasa Ikeda, Ichiro Hashimoto, Toshiaki Tamaki, Yuki Izawa-Ishizawa
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 142 Issue: 3 Pages: 109-115

    • DOI

      10.1016/j.jphs.2019.12.005

    • NAID

      120006980541

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Search for therapeutic agents for cardiac arrest using a drug discovery tool and large-scale medical information database2019

    • Author(s)
      Yoshito Zamami, Takahiro Niimura, Toshihiro Koyama, Yuta Shigemi, Yuki Izawa-Ishizawa, Ayako Ohshima, Keisaku Harada, Toru Imai, Hiromi Hagiwara, Naoto Okada, Mitsuhiro Goda, Kenshi Takechi, Masayuki Chuma, Koichiro Tsuchiya, Yutaka Kondo, Shiro Hinotsu, Mitsunobu R Kano, Keisuke Ishizawa
    • Journal Title

      Frontiers in Pharmacology

      Volume: 10 Pages: 109-115

    • DOI

      10.3389/fphar.2019.01257

    • NAID

      120006859989

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a novel aortic dissection mouse model and evaluation of drug efficacy using in-vivo assays and database analyses2019

    • Author(s)
      Izawa-Ishizawa Yuki、Imanishi Masaki、Zamami Yoshito、Toya Hiroki、Nagao Tomoko、Morishita Marin、Tsuneyama Koichi、Horinouchi Yuya、Kihira Yoshitaka、Takechi Kenshi、Ikeda Yasumasa、Tsuchiya Koichiro、Yoshizumi Masanori、Tamaki Toshiaki、Ishizawa Keisuke
    • Journal Title

      Journal of Hypertension

      Volume: 37 Issue: 1 Pages: 73-83

    • DOI

      10.1097/hjh.0000000000001898

    • NAID

      120006627861

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Renoprotective effects of a factor Xa inhibitor: fusion of basic research and a database analysis2018

    • Author(s)
      Horinouchi Yuya、Ikeda Yasumasa、Fukushima Keijo、Imanishi Masaki、Hamano Hirofumi、Izawa-Ishizawa Yuki、Zamami Yoshito、Takechi Kenshi、Miyamoto Licht、Fujino Hiromichi、Ishizawa Keisuke、Tsuchiya Koichiro、Tamaki Toshiaki
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 10858-10858

    • DOI

      10.1038/s41598-018-29008-2

    • NAID

      120006535061

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nitrosonifedipine, a photodegradation product of nifedipine, suppresses pharmacologically induced aortic aneurysm formation2018

    • Author(s)
      Imanishi Masaki、Izawa-Ishizawa Yuki、Sakurada Takumi、Kohara Yusuke、Horinouchi Yuya、Sairyo Eriko、Zamami Yoshito、Takechi Kenshi、Chuma Masayuki、Fukushima Keijo、Ikeda Yasumasa、Fujino Hiromichi、Yoshizumi Masanori、Tsuchiya Koichiro、Tamaki Toshiaki、Ishizawa Keisuke
    • Journal Title

      Pharmacology

      Volume: 102 Issue: 5-6 Pages: 287-299

    • DOI

      10.1159/000492577

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Xanthine oxidase inhibition by febuxostat in macrophages suppresses angiotensin II-induced aortic fibrosis2018

    • Author(s)
      Kondo Masateru、Imanishi Masaki、Fukushima Keijo、Ikuto Raiki、Murai Yoichi、Horinouchi Yuya、Izawa-Ishizawa Yuki、Goda Mitsuhiro、Zamami Yoshito、Takechi Kenshi、Chuma Masayuki、Ikeda Yasumasa、Fujino Hiromichi、Tsuchiya Koichiro、Ishizawa Keisuke
    • Journal Title

      American Journal of Hypertension

      Volume: 32 Issue: 3 Pages: 249-256

    • DOI

      10.1093/ajh/hpy157

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 薬剤誘発性急性大動脈疾患に対するケルセチンの抑制効果2020

    • Author(s)
      近藤 正輝, 石澤 有紀, 合田 光寛, 鈴木 琴子, 松岡 里英, 座間味 義人, 中馬 真幸, 池田 康将, 石澤 啓介
    • Organizer
      第137回日本薬理学会近畿部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ビッグデータ解析と基礎研究を融合した新たな研究手法による腫瘍循環器学へのアプローチ2020

    • Author(s)
      石澤 有紀, 座間味 義人, 新村 貴博, 合田 光寛, 八木 健太, 中馬 真幸, 今西 正樹, 石澤 啓介
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 医療ビッグデータを活用したドラッグリポジショニング研究2020

    • Author(s)
      座間味 義人, 新村 貴博, 石澤 有紀, 合田 光寛, 濱野 裕章, 岡田 直人, 八木 健太, 中馬 真幸, 桐野 靖, 中村 敏己, 石澤 啓介
    • Organizer
      第30回日本医療薬学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 薬剤誘発性急性大動脈疾患に対するケルセチンの効果2019

    • Author(s)
      鈴木琴子, 石澤 有紀, 合田 光寛, 近藤 正輝, 今西 正樹, 座間味 義人, 堀ノ内 裕也, 武智 研志, 中馬 真幸, 池田 康将, 石澤 啓介
    • Organizer
      第135回日本薬理学会近畿部会
    • Related Report
      2019 Research-status Report
  • [Presentation] キサンチンオキシダーゼ阻害剤による新規血管線維化抑制機構の検討2019

    • Author(s)
      近藤 正輝, 今西 正樹, 生藤 来希, 村井 陽一, 福島 圭譲, 堀ノ内 裕也, 石澤 有紀, 合田 光寛, 座間味 義人, 武智 研志, 中馬 真幸, 池田 康将, 藤野 裕道, 土屋 浩一郎, 石澤 啓介
    • Organizer
      日本薬学会第139年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 大規模医療情報を用いたニコランジルの心肺停止後予後改善効果の検討2019

    • Author(s)
      新村 貴博, 座間味 義人, 石澤 有紀, 合田 光寛, 武智 研志, 中馬 真幸, 福島 圭穣, 堀ノ内 裕也, 池田 康将, 藤野 裕道, 土屋 浩一郎, 石澤 啓介
    • Organizer
      医療薬学フォーラム2019/第27回クリニカルファーマシーシンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Development of therapeutic agents using drug discovery tools and large-scale medical information2019

    • Author(s)
      Yoshito Zamami, Yuki Izawa-Ishizawa, Takahiro Niimura, Mitsuhiro Goda, Naoto Okada, Kenshi Takechi, Masayuki Chuma, Keijo Fukushima, Yuya Horinouchi, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Keisuke Ishizawa
    • Organizer
      FIP2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] リアルワールドビッグデータを活用した新規腎保護薬の探索2018

    • Author(s)
      堀ノ内 裕也, 池田 康将, 福島 圭穣, 濱野 裕章, 今西 正樹, 石澤 有紀, 座間味 義人, 武智 研志, 藤野 裕道, 石澤 啓介, 土屋 浩一郎, 玉置 俊晃
    • Organizer
      第28回日本医療薬学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] 線維芽細胞特異的 ERK5欠損は angiotensin II 誘発性心臓線維化を亢進させる2018

    • Author(s)
      今西 正樹, 近藤 正輝, 山川 裕介, 生藤 来希, 村井 陽一, 座間味 義人, 武智 研志, 中馬 真幸, 堀ノ内 裕也, 福島 圭穣, 石澤 有紀, 池田 康将, 藤野 裕道, 土屋 浩一郎, 石澤 啓介
    • Organizer
      第41回日本高血圧学会総会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efect of nicorandil on survival of patients with cardiac arrest using large-scale medical claims database2018

    • Author(s)
      Takahiro Niimura1, Yoshito Zamami1,2, Yuki Izawa-Ishizawa3, Kenshi Takechi4, Masaki Imanishi2, Yuya Horinouchi3, Yasumasa Ikeda3, Koichiro Tsuchiya5, Toshiaki Tamaki3, Keisuke Ishizawa
    • Organizer
      WCP2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Febuxostat ameliorates angiotensin II-induced aortic fibrosis via suppressing macrophage-derived TGF-β expression2018

    • Author(s)
      Masaki Imanishi, Masateru Kondo, Yoshito Zamami, Kenshi Takechi, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa
    • Organizer
      WCP2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Drug repositioning for post cardiopulmonary resuscitation syndrome using large-scale medical claims2018

    • Author(s)
      Yoshito Zamami, Yuki Izawa-Ishizawa, Takahiro Niimura, Kenshi Takechi, Masaki Imanishi, Masayuki Chuma, Yuya Horinouchi, Yasumasa Ikeda, Koichiro Tsuchiya, Keisuke Ishizawa
    • Organizer
      FIP2018
    • Related Report
      2018 Research-status Report
  • [Presentation] 薬物誘発性大動脈瘤または大動脈解離モデルマウスに対するケルセチンの効果2018

    • Author(s)
      鈴木 琴子, 石澤 有紀, 近藤 正輝, 今西 正樹, 座間味 義人, 堀ノ内 裕也, 武智 研志, 合田 光寛, 中馬 真幸, 池田 康将, 石澤 啓介
    • Organizer
      第92回日本薬理学会年会
    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi