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The pathophysiological mechanisms and causative genetic mutations of familial aortic aneusyrm/dissection and patent ductus arteriosus

Research Project

Project/Area Number 18K08083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53020:Cardiology-related
Research InstitutionJichi Medical University

Principal Investigator

Imai Yasushi  自治医科大学, 医学部, 教授 (20359631)

Co-Investigator(Kenkyū-buntansha) 永井 良三  自治医科大学, 医学部, 学長 (60207975)
相澤 健一  自治医科大学, 医学部, 准教授 (70436484)
高橋 政夫  自治医科大学, 医学部, 講師 (00447418)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords大動脈解離 / 大動脈瘤 / 動脈管開存症 / 遺伝子改変マウス / 臨床遺伝子診断 / Myh11 / 動脈管開存 / Crisper-Cas9 / モデルマウス / パネル遺伝子解析 / マルファン症候群 / 血管型ミオシン / ヒトゲノム解析 / 家族性・遺伝性 / 大動脈解離・瘤 / 先天性心疾患 / 心不全
Outline of Final Research Achievements

We generated gene-engineered mice carrying a MYH11 causative mutation, which was detected in a Japanese pedigree with familial aortic dissection. We demonstrated that the heterozygous mice tended to suffer from aortic dissection in the Angiotensin II infusion model and the homozygous mice were complicated with aortic dissection and patent ductus arteriosus. Therefore, this mutant mouse is a promising animal model for hereditary aortic dissection in the field of cardiovascular medicine and pharmacology. In addition, we also performed genetic analyses for the patients with aortic aneurysm/dissection. We could detect causative genetic mutations in most of the cases, suggesting feasibility and importance of clinical genome sequencing for the aforementioned diseases.

Academic Significance and Societal Importance of the Research Achievements

家族性大動脈解離・瘤について予防・治療における管理・薬物療法は未確立である。そのため、ヒト家系に見出された遺伝子変異を組み入れ、表現型を再現する動物モデルを構築し得たことの意義は大きく、難病の治療解明へ大きく寄与することが期待される。さらに大動脈解離・瘤症例における臨床的遺伝子診断も我々の小規模の検討においては有用であった。大動脈疾患への基礎・臨床両面からのアプローチが今後も求められる。

Report

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

    (15 results)

All 2021 2020 2019 2018

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (5 results)

  • [Journal Article] Percutaneous Atrial Septal Defect Closure in Adult Ebstein's Anomaly with Exertional Hypoxemia2020

    • Author(s)
      Kensuke Oka, Mitsuru Seki, Koichi Kataoka, Tomoyuki Sato, Yasushi Imai, Takanori Yamagata
    • Journal Title

      International Heart Journal

      Volume: 61 Issue: 3 Pages: 620-623

    • DOI

      10.1536/ihj.19-641

    • NAID

      130007849572

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2020-05-30
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Novel Concept in AVNRT2020

    • Author(s)
      Watanabe Tomonori、Imai Yasushi
    • Journal Title

      International Heart Journal

      Volume: 61 Issue: 2 Pages: 199-200

    • DOI

      10.1536/ihj.20-066

    • NAID

      130007821437

    • ISSN
      1349-2365, 1349-3299
    • Year and Date
      2020-03-28
    • Related Report
      2020 Annual Research Report
  • [Journal Article] Ethnic differences in association of outcomes with trimethylamine N‐oxide in acute heart failure patients2020

    • Author(s)
      Yazaki Yoshiyuki、Aizawa Kenichi、Israr Muhammad Zubair、Negishi Keita、Salzano Andrea、Saitoh Yuka、Kimura Natsuka、Kono Ken、Heaney Liam、Cassambai Shabana、Bernieh Dennis、Lai Florence、Imai Yasushi、Kario Kazuomi、Nagai Ryozo、Ng Leong L.、Suzuki Toru
    • Journal Title

      ESC Heart Failure

      Volume: 7 Issue: 5 Pages: 2373-2378

    • DOI

      10.1002/ehf2.12777

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Methotrexate for placenta accreta spectrum disorders: Is it needed?2020

    • Author(s)
      Matsubara Shigeki、Takahashi Hironori、Takei Yuji、Imai Yasushi
    • Journal Title

      Journal of Clinical Pharmacy and Therapeutics

      Volume: 45 Issue: 2 Pages: 399-400

    • DOI

      10.1111/jcpt.13120

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Glycolysis and subsequent mevalonate biosynthesis play an important role in Th2 cell differentiation.2020

    • Author(s)
      Yagi Y, Kuwahara M, Suzuki J, Imai Y and Yamashita M.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 530 Issue: 2 Pages: 355-361

    • DOI

      10.1016/j.bbrc.2020.08.009

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of clock gene Dbp in omental and mesenteric adipose tissue in patients with type 2 diabetes2020

    • Author(s)
      Ushijima Kentaro、Suzuki Chisato、Kitamura Hiroko、Shimada Ken、Kawata Hirotoshi、Tanaka Akira、Horie Hisanaga、Hosoya Yoshinori、Imai Yasushi、Yamashita Chikamasa、Fujimura Akio
    • Journal Title

      BMJ Open Diabetes Research & Care

      Volume: 8 Issue: 1 Pages: e001465-e001465

    • DOI

      10.1136/bmjdrc-2020-001465

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Association between P wave polarity in atrial premature complexes and cardiovascular events in a community-dwelling population2020

    • Author(s)
      Kabutoya Tomoyuki、Imai Yasushi、Ishikawa Shizukiyo、Kario Kazuomi
    • Journal Title

      BMJ Open

      Volume: 10 Issue: 11 Pages: e033553-e033553

    • DOI

      10.1136/bmjopen-2019-033553

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Time Course of Left Ventricular Pseudoaneurysm After Catheter Ablation of LVOT Tachycardia2020

    • Author(s)
      Watanabe Tomonori、Imai Yasushi、Morita Eri、Okuyama Takafumi、Watanabe Hiroaki、Yokota Ayako、Komori Takahiro、Kabutoya Tomoyuki、Shimpo Masahisa、Hachiya Hitoshi、Kario Kazuomi
    • Journal Title

      JACC: Clinical Electrophysiology

      Volume: 6 Issue: 2 Pages: 248-249

    • DOI

      10.1016/j.jacep.2019.11.011

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Indomethacin reduces rates of aortic dissection and rupture of the abdominal aorta by inhibiting monocyte/macrophage accumulation in a murine model2019

    • Author(s)
      Tomida S, Aizawa K, Nishida N, Aoki H, Imai Y, Nagai R, Suzuki T.
    • Journal Title

      Sci Rep

      Volume: 24 Issue: 1 Pages: 10751-10751

    • DOI

      10.1038/s41598-019-46673-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Impact of Pathogenic FBN1 Variant Types on the Progression of Aortic Disease in Patients With Marfan Syndrome.2018

    • Author(s)
      Takeda N, Inuzuka R, Maemura S, Morita H, Nawata K, Fujita D, Taniguchi Y, Yamauchi H, Yagi H, Kato M, Nishimura H, Hirata Y, Ikeda Y, Kumagai H, Amiya E, Hara H, Fujiwara T, Akazawa H, Suzuki JI, Imai Y, Nagai R, Takamoto S, Hirata Y, Ono M, Komuro I.
    • Journal Title

      Circ Genom Precis Med

      Volume: 11

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] マルファン症候群・家族性大動脈解離 up-to-date2021

    • Author(s)
      今井靖
    • Organizer
      日本成人先天性心疾患学会 webinar All stars
    • Related Report
      2020 Annual Research Report
  • [Presentation] 成人先天性心疾患治療介入に必要な知識2021

    • Author(s)
      今井靖
    • Organizer
      第85回日本循環器学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 重症大動脈弁閉鎖不全・心不全から回復し良好に経過したマルファン症候群の一例2020

    • Author(s)
      芳野真子、今井靖、根岸経太、大木伸一、川人宏次、苅尾七臣
    • Organizer
      第255回日本循環器学会関東甲信越地方会
    • Related Report
      2020 Annual Research Report
  • [Presentation] A novel mouse model of familial thoracic aortic aneurysms and dissections with a deletion mutation in Myh112019

    • Author(s)
      根岸経太、相澤健一、今井靖、永井良三
    • Organizer
      第40回日本臨床薬理学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] A Deletion Mutation in Myosin Heavy Chain MYH11 Reduces the Contraction Force of the Aorta Resulting in Aortic Dissection2019

    • Author(s)
      Negishi K, Aizawa K, Imai Y et al.
    • Organizer
      第83回日本循環器学会学術集会
    • Related Report
      2018 Research-status Report

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

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