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Development of novel aortic dissection model based on vascular endothelial dysfunction and elucidation of pathophysiological mechanisms

Research Project

Project/Area Number 15K07967
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pharmacology in pharmacy
Research InstitutionThe University of Tokushima

Principal Investigator

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

Co-Investigator(Kenkyū-buntansha) 石澤 有紀  徳島大学, 大学院医歯薬学研究部(医学系), 講師 (40610192)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords動脈硬化 / 大動脈解離 / 血管内皮
Outline of Final Research Achievements

In the present study, we have succeeded to establish a novel acute aortic dissection model mouse. Aortic dissection in C57Bl/6J mouse is induced by the combined usage of Nω-nitro-L-arginine methyl ester (L-NAME), angiotensin II (Ang II), and β-aminopropionitrile (BAPN). L-NAME induces endothelial cell damage. Administration of Ang II elevated systolic blood pressure. BAPN is one of the lysyloxidase inhibitor, which causes vessel medial fragility. We named this model “LAB” model. Pitavastatin, an HMG-CoA inhibitor used as lipid lowering agent, suppressed the incidence of aortic dissection. From the results of in vitro analysis using cultured human umbilical vein endothelial cells, pitavastatin effects are mediated by extracellular signal-regulated kinase 5 (ERK5) activation. Our findings suggested that this novel “LAB” model are useful to examine the pathophysiology of aortic dissection and the estimation of the drug efficacy against aortic dissection.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (32 results)

All 2017 2016 2015

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 14 results,  Open Access: 14 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 9 results)

  • [Journal Article] Dietary iron restriction alleviates renal tubulointerstitial injury induced by protein overload in mice2017

    • Author(s)
      Yasumasa Ikeda, Yuya Horinouchi, Hirofumi Hamano, Tasuku Hirayama, Seiji Kishi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Ken-ichi Aihara, Hideko Nagasawa, Koichiro Tsuchiya, and Toshiaki Tamaki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 10621-10621

    • DOI

      10.1038/s41598-017-11089-0

    • NAID

      120006534998

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pharmacological approach for drug repositioning against cardiorenal diseases2017

    • Author(s)
      Zamami Y, Imanishi M, Takechi K, Ishizawa K
    • Journal Title

      The Journal of Medical Investigation

      Volume: 64 Issue: 3.4 Pages: 197-201

    • DOI

      10.2152/jmi.64.197

    • NAID

      130006105190

    • ISSN
      1343-1420, 1349-6867
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrocortisone administration was associated with improved survival in Japanese patients with cardiac arrest.2017

    • Author(s)
      48)Niimura T, Zamami Y, Koyama T, Izawa-Ishizawa Y, Miyake M, Koga T, Harada K, Ohshima A, Imai T, Kondo Y, Imanishi M, Takechi K, Fukushima K, Horinouchi Y, Ikeda Y, Fujino H, Tsuchiya K, Tamaki T, Hinotsu S, Kano MR, Ishizawa K.
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 17919-17919

    • DOI

      10.1038/s41598-017-17686-3

    • NAID

      120006535027

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Iron-induced skeletal muscle atrophy involves an Akt-forkhead box O3-E3 ubiquitin ligase-dependent pathway.2016

    • Author(s)
      Yasumasa Ikeda, Mizuki Imao, Akiho Satoh, Hiroaki Watanabe, Hirofumi Hamano, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki
    • Journal Title

      Journal of Trace Elements in Medicine and Biology

      Volume: 35 Pages: 66-76

    • DOI

      10.1016/j.jtemb.2016.01.011

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Clinical Evaluation of Pharmacist Interventions in Patients Treated with Anti-methicillin-Resistant <i>Staphylococcus aureus</i> Agents in a Hematological Ward2016

    • Author(s)
      Naoto Okada, Shuji Fushitani, Momoyo Azuma, Shingen Nakamura, Toshimi Nakamura, Kazuhiko Teraoka, Hiroyoshi Watanabe, Masahiro Abe, Kazuyoshi Kawazoe, Keisuke Ishizawa
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 39 Issue: 2 Pages: 295-300

    • DOI

      10.1248/bpb.b15-00774

    • NAID

      130005122366

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Angiotensin II alters the expression of duodenal iron transporters, hepatic hepcidin, and body iron distribution in mice2015

    • Author(s)
      Soichiro Tajima, Yasumasa Ikeda, Hideaki Enomoto, Imao Mizuki, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Rihito Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki
    • Journal Title

      European Journal of Nutrition

      Volume: 印刷中 Issue: 5 Pages: 709-719

    • DOI

      10.1007/s00394-014-0749-1

    • NAID

      120006732013

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Spontaneously hyperactive MEK-Erk pathway mediates paradoxical facilitation of cell proliferation in mild hypoxia.2015

    • Author(s)
      Miyamoto L, Yagi Y, Hatano A, Kawazoe K, Ishizawa K, Minakuchi K, Tomita S, Tsuchiya K.
    • Journal Title

      Biochim Biophys Acta

      Volume: 1850 Issue: 4 Pages: 640-646

    • DOI

      10.1016/j.bbagen.2014.12.006

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A Long-Term High-Fat Diet Changes Iron Distribution in the Body, Increasing Iron Accumulation Specifically in the Mouse Spleen2015

    • Author(s)
      Noriko Yamano, Yasumasa Ikeda, Minoru Sakama, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Licht Miyamoto, Shuhei Tomita, Koichiro Tsuchiya, Toshiaki Tamaki
    • Journal Title

      Journal of Nutritional Science and Vitaminology

      Volume: 61 Issue: 1 Pages: 20-27

    • DOI

      10.3177/jnsv.61.20

    • NAID

      130005070829

    • ISSN
      0301-4800, 1881-7742
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Characteristics and risk factors of interstitial lung disease induced by chemotherapy for lung cancer2015

    • Author(s)
      Takumi Sakurada, Soji Kakiuchi, Soichiro Tajima, Yuya Horinouchi, Naoto Okada, Hirotaka Nishisako, Toshimi Nakamura, Kazuhiko Teraoka, Kazuyoshi Kawazoe, Hiroaki Yanagawa, Yasuhiko Nishioka, Kazuo Minakuchi, Keisuke Ishizawa
    • Journal Title

      The Annals Pharmacotherapy

      Volume: 49(4) Issue: 4 Pages: 398-404

    • DOI

      10.1177/1060028014566446

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia Decreases Glucagon-Like Peptide-1 Secretion from the GLUTag Cell Line2015

    • Author(s)
      Yoshitaka Kihira, Ariunzaya Burentogtokh, Mari Itoh, Yuki Izawa-Ishizawa, Keisuke Ishizawa, Yasumasa Ikeda, Koichiro Tsuchiya, and Toshiaki Tamaki
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 4 Pages: 514-521

    • DOI

      10.1248/bpb.b14-00612

    • NAID

      130005062264

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway2015

    • Author(s)
      Yasumasa Ikeda, Hamano Hirofumi, Satoh Akiho, Horinouchi Yuya, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki
    • Journal Title

      Hypertension Research

      Volume: 38(11) Issue: 11 Pages: 733-740

    • DOI

      10.1038/hr.2015.74

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ephedra protects vascular endothelium cells from vinorelbine-induced cytotoxicity by preserving endothelial nitric oxide synthase activity2015

    • Author(s)
      Ken Konaka, Kouta Moriyama, Naoto Okada, Takahiro Nishisako, Masayuki Syono, Kazuyoshi Kawazoe, Keisuke Ishizawa
    • Journal Title

      Traditional & Kampo Medicine

      Volume: 2 Issue: 2 Pages: 274-280

    • DOI

      10.1002/tkm2.1024

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pemetrexed-Induced Rash May Be Prevented by Supplementary Corticosteroids2015

    • Author(s)
      Takumi Sakurada, Soji Kakiuchi, Soichiro Tajima, Yuya Horinouchi, Ken Konaka, Naoto Okada, Hirotaka Nishisako, Toshimi Nakamura, Kazuhiko Teraoka, Kazuyoshi Kawazoe, Hiroaki Yanagawa, Yasuhiko Nishioka, Keisuke Ishizawa
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 11 Pages: 1752-1756

    • DOI

      10.1248/bpb.b15-00435

    • NAID

      130005106388

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Japanese Physicians' Views on Drug Post-Marketing Surveillance2015

    • Author(s)
      Kazuki Maeda, Rumi Katashima, Keisuke Ishizawa, Hiroaki Yanagawa
    • Journal Title

      J Clin Med Res

      Volume: 7 Issue: 12 Pages: 956-960

    • DOI

      10.14740/jocmr2328w

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] フェブキソスタットはアンジオテンシンII誘発性大動脈線維化を抑制する2017

    • Author(s)
      今西正樹、田中恭平、生藤来希、座間味 義人、武智研志、堀ノ内裕也、 石澤有紀、池田康将、藤野裕道、土屋浩一郎、玉置俊晃、石澤啓介
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール(長崎県長崎市)
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Angiotensin II誘発性血管リモデリングに対するfebuxostatの効果2017

    • Author(s)
      今西正樹、田中恭平、生藤来希、座間味義人、武智研志、堀ノ内裕也、 石澤有紀、池田康将、藤野裕道、土屋浩一郎、玉置俊晃、石澤啓介
    • Organizer
      第46回日本心脈管作動物質学会
    • Place of Presentation
      琉球大学(沖縄県中頭郡)
    • Year and Date
      2017-02-10
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] インドキシル硫酸はヘプシジンを介した鉄代謝異常に関与する2017

    • Author(s)
      濱野裕章、池田康将、渡邉大晃、堀ノ内裕也、石澤有紀、石澤啓介、土屋浩一郎、玉置俊晃
    • Organizer
      第60回日本腎臓学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The effects of febuxostat on angiotensin II-induced vascular remodeling2017

    • Author(s)
      Masaki Imanishi, Kyohei Tanaka, Raiki Ikuto, Yoshito Zamami, Kenshi Takechi, Yuya Horinouchi, Yuki Ishizawa, Yasumasa Ikeda, Hiromichi Fujino, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa
    • Organizer
      European Meeting of Hypertension and Cardiovascular Protection
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 急性大動脈解離易発症マウスにおけるquercetinの効果2017

    • Author(s)
      鍵本優有、石澤有紀、細岡真由子、斎藤尚子、鈴木琴子、今西正樹、 堀ノ内裕也、座間味義人、武智研志、池田康将、土屋浩一郎、玉置俊晃、 石澤啓介
    • Organizer
      第56回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Indoxyl Sulfate Disturbs Normal Iron Metabolism via Hepcidin Upregulation in Chronic Kidney Disease2017

    • Author(s)
      Hirofumi Hamano, Yasumasa Ikeda, Hiroaki Watanabe, Yuya Horinouchi, Yuki Izawa-Ishizawa, Masaki Imanishi, Yoshito Zamami, Kenshi Takechi, Licht Miyamoto, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki
    • Organizer
      ASN Kidney Week 2017 Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ケルセチンによる動脈硬化性疾患発症に対する予防効果の検討2017

    • Author(s)
      石澤有紀、鍵本優有、今西正樹、堀ノ内裕也、鈴木琴子、岩田悠佑、座間味義人、武智研志、池田康将、玉置俊晃、石澤啓介
    • Organizer
      第27回日本循環薬理学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Topical Application of Nitrosonifedipine, a Novel Free Radical Scavenger, Ameliorate the Ischemic Skin Flap Necrosis2016

    • Author(s)
      Yutaka Fukunaga, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Yasumasa Ikeda, Keisuke Ishizawa, Koichiro Tsuchiya, Toshiaki Tamaki, Ichiro Hashimoto
    • Organizer
      Plastic Surgery THE MEETING 2016
    • Place of Presentation
      ロサンゼルス(アメリカ)
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳卒中後の神経症状増悪に対するニトロソニフェジピンの効果2016

    • Author(s)
      今西 正樹, 石澤 有紀, 座間味 義人, 田淵 正樹, 玉置 俊晃, 石澤 啓介
    • Organizer
      第46回日本神経精神薬理学会年会
    • Place of Presentation
      ソウル(韓国)
    • Year and Date
      2016-07-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The effects of pitavastatin, a lipid-lowering agent, against aortic dissection model mice induced by L-NAME, a nitric oxide synthase inhibitor2016

    • Author(s)
      Yuki Izawa-Ishizawa, Masaki Imanishi, Yuya Horinouchi, Kenshi Takechi, Yoshito Zamami, Yasumasa Ikeda, Koichiro Tsuchiya, Toshiaki Tamaki, Keisuke Ishizawa
    • Organizer
      The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] The Involvement of Iron Supplementation on Erythropoietin Expression2016

    • Author(s)
      Yasumasa Ikeda, Keisuke Oshima, Yuya Horinouchi, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Koichiro Tsuchiya and Toshiaki Tamaki
    • Organizer
      Experimental Biology 2016
    • Place of Presentation
      サンディエゴ(アメリカ)
    • Year and Date
      2016-04-02
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 無機リン刺激による血管平滑筋細胞石灰化におけるrho-kinase 及び cyclophilinA の関与2016

    • Author(s)
      鍵本 優有, 石澤 有紀, 今西 正樹, 座間味 義人, 木平 孝高, 池田 康将, 土屋 浩一郎, 玉置 俊晃, 石澤 啓介
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of endothelial dysfunction-induced aortic dissection model and search for a preventive strategy2016

    • Author(s)
      石澤 有紀, 今西 正樹, 木平 孝高, 宮本 理人, 座間味 義人, 池田 康将, 玉置 俊晃, 土屋 浩一郎, 石澤 啓介
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 高リン刺激は血管平滑筋細胞においてrho-kinase-cyclophilin A経路を活性化させる,2016

    • Author(s)
      石澤 有紀, 石澤 啓介, 鍵本 優有, 斎藤 尚子, 高田 真衣, 木平 孝高, 今西 正樹, 池田 康将, 土屋 浩一郎, 玉置 俊晃
    • Organizer
      第45回日本心脈管作動物質学会
    • Place of Presentation
      阿波観光ホテル(徳島県・徳島市)
    • Year and Date
      2016-02-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 大動脈瘤形成における平滑筋由来HIF-1αの役割2016

    • Author(s)
      今西正樹、松永慎司、石澤啓介、玉置俊晃、冨田修平
    • Organizer
      第26回日本循環薬理学会
    • Place of Presentation
      信州大学(長野県松本市)
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 大動脈解離発症における内皮障害の関与2015

    • Author(s)
      斎藤 尚子, 石澤 有紀, 石澤 啓介, 戸谷 紘基, 今西 正樹, 鍵本 優有, 細岡 真由子, 木平 孝高, 池田 康将, 土屋 浩一郎, 玉置 俊晃
    • Organizer
      第25回日本循環薬理学会
    • Place of Presentation
      東大寺総合文化センター(奈良県・奈良市)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 大動脈解離発症における内皮障害の関与の検討2015

    • Author(s)
      戸谷 紘基, 石澤 啓介, 石澤 有紀, 細岡 真由子, 鍵本 優有, 斎藤 尚子, 宮本 理人, 木平 孝高, 池田 康将, 玉置 俊晃, 土屋 浩一郎
    • Organizer
      第54回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Place of Presentation
      高知市文化プラザ、かるぽーと(高知県・高知市)
    • Year and Date
      2015-10-31
    • Related Report
      2015 Research-status Report
  • [Presentation] 血管石灰化シグナルにおけるRhoキナーゼおよびサイクロフィリンAの関与2015

    • Author(s)
      石澤 有紀, 石澤 啓介, 大越 瑞穂, 土肥 紗希子, 木平 孝高, 池田 康将, 玉置 俊晃
    • Organizer
      第47回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      仙台国際センター(宮城県・仙台市)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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