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Pharmacological and mechanical approach to the prevention of the aortic aneurysm dilatation and rupture

Research Project

Project/Area Number 18H02886
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 55030:Cardiovascular surgery-related
Research InstitutionThe University of Tokyo

Principal Investigator

Hoshina Katsuyuki  東京大学, 医学部附属病院, 准教授 (90571761)

Co-Investigator(Kenkyū-buntansha) 大島 まり  東京大学, 大学院情報学環・学際情報学府, 教授 (40242127)
山本 創太  芝浦工業大学, 工学部, 教授 (80293653)
高山 利夫  東京大学, 医学部附属病院, 講師 (80802694)
山本 晃太  東京大学, 医学部附属病院, 登録研究員 (00753542)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥14,040,000 (Direct Cost: ¥10,800,000、Indirect Cost: ¥3,240,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
KeywordsDrug delivery system / 大動脈瘤 / ナノ粒子 / ピタバスタチン / シミュレーション / simulation / aneurysm model / hemodynamic / nano praticle / drug delivery system / 腹部大動脈瘤 / 動物モデル / Drug Delivery System / 高分子ミセル
Outline of Final Research Achievements

Using the aortic aneurysm model of rat, we attempted to construct a drug delivery system using nanomicelles. The drugs contained in nanomicelles have been limited by electric charge, but now it is possible to include statins. Statins are therapeutic agents for hyperlipidemia and also have anti-inflammatory effects. The pitavastatin-encapsulating micelles were found to be accumulated in abdominal aortic aneurysm pathologically, and we found that the micelle prevented the aneurysm expansion.
At the same time, a simulation of aortic blood flow was performed to examine how nanomicelles behaved in the aneurysm, and the concentration gradient was successfully visualized. However, the action of micelles on the wall has just begun to be examined microscopically. We are moving to simulating drug efficiency at the site of the aneurysm.

Academic Significance and Societal Importance of the Research Achievements

薬剤の投与方法は注射や内服があるが、薬剤毒性を考えると容量に限界がある。病変部に限局して到達する方法として、ナノ粒子を用いた薬剤投与を検討してきた。スタチン、特にピタバスタチンは日本人のデータが多くある抗脂質薬で、抗炎症作用も併せ持ち心血管イベントも減らすデータがある。これを内包したナノ粒子の挙動をシミュレートできれば、より臨床応用に近づくと考えられる。動物モデルから毒性が少ないことが今回わかり、また動脈瘤の形状によって、その作用する部位や量が想定できれば、オーダーメイドの治療につながると考えられる。

Report

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

    (9 results)

All 2020 2019 Other

All Journal Article (5 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (3 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Efficient Suppression of Abdominal Aortic Aneurysm Expansion in Rats through Systemic Administration of Statin-Loaded Nanomedicine2020

    • Author(s)
      Natsumi Fukuhara, Yuto Honda, Nao Ukita, Makoto Matsui, Yutaka Miura, Katsuyuki Hoshina
    • Journal Title

      Int J Mol Sci

      Volume: 21 Issue: 22 Pages: 8702-8702

    • DOI

      10.3390/ijms21228702

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hemodynamic Simulation of Pancreaticoduodenal Artery Aneurysm Formation Using an Electronic Circuit Model and a Case Series Analysis2019

    • Author(s)
      Miyahara Kazuhiro、Hoshina Katsuyuki、Nitta Jun、Kimura Masaru、Yamamoto Sota、Ohshima Marie
    • Journal Title

      Annals of Vascular Diseases

      Volume: 12 Issue: 2 Pages: 176-181

    • DOI

      10.3400/avd.oa.19-00005

    • NAID

      130007667034

    • ISSN
      1881-641X, 1881-6428
    • Year and Date
      2019-06-25
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Quantification of Abdominal Aortic Aneurysm Calcification Using the Agatston Method Can Predict Accelerated Expansion Rate2019

    • Author(s)
      Nakayama Atsuko、Morita Hiroyuki、Hoshina Katsuyuki、Komuro Issei
    • Journal Title

      Circulation Journal

      Volume: 83 Issue: 3 Pages: 689

    • DOI

      10.1253/circj.CJ-18-0576

    • NAID

      130007604268

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2019-02-25
    • Related Report
      2019 Annual Research Report
  • [Journal Article] Computational simulation of flow-induced arterial remodeling of the pancreaticoduodenal arcade associated with celiac artery stenosis2019

    • Author(s)
      Yuhn Changyoung、Hoshina Katsuyuki、Miyahara Kazuhiro、Oshima Marie
    • Journal Title

      Journal of Biomechanics

      Volume: 92 Pages: 146-154

    • DOI

      10.1016/j.jbiomech.2019.05.043

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Changes in blood flow distribution after hypogastric artery embolization and the ischaemic tolerance of the pelvic circulation2019

    • Author(s)
      Nitta Jun、Hoshina Katsuyuki、Isaji Toshihiko
    • Journal Title

      Medicine

      Volume: 98 Issue: 5 Pages: e14214-e14214

    • DOI

      10.1097/md.0000000000014214

    • Related Report
      2019 Annual Research Report
  • [Presentation] Computational simulation of vascular remodeling of the pancreaticoduodenal arcades in the presence of celiac artery stenosis2019

    • Author(s)
      Yuhn C, Miyahara K, Hoshina K, Kobayashi M, Oshima M.
    • Organizer
      8th World Congress of Biomechanics
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Impact of sacrifice of the inferior mesenteric artery or the internal iliac artery in abdominal aortic aneurysm surgery in colorectal cancer resection case.2019

    • Author(s)
      Akai T, Okata S, Matsuura S, Hanada K, Sano M, Ohashi Y, Miyahara K, Fukuhara N, Isaji T, Takayama T, Hoshina K
    • Organizer
      International Union of Angiology, Japan Chapter Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Endovascular Treatment of Internal Iliac Artery Aneurysm with Gore IBE system2019

    • Author(s)
      Takayama T, Shirasu T, Kimura M, Matsuura S, Hanada K, Okata S, Sano M, Miyahara K, Fukuhara N, Isaji T, Akai T, Hoshina K
    • Organizer
      International Union of Angiology, Japan Chapter Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 東京大学血管外科 研究

    • URL

      https://vascular-1su.jp/research/

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report

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

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