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Basic research of prevention and intervention for congenital cardiac outflow tract defects using animal models

Research Project

Project/Area Number 25293238
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Pediatrics
Research InstitutionKeio University

Principal Investigator

Yamagishi Hiroyuki  慶應義塾大学, 医学部, 准教授 (40255500)

Co-Investigator(Kenkyū-buntansha) TSUCHIHASHI TAKATOSHI  慶應義塾大学, 医学部, 共同研究員 (10286528)
MAKINO SHINJI  慶應義塾大学, 医学部, 准教授 (20306707)
UCHIDA KEIKO  慶應義塾大学, 保健管理センター, 講師 (50286522)
YUASA SHINSUKE  慶應義塾大学, 医学部, 准教授 (90398628)
Co-Investigator(Renkei-kenkyūsha) IEDA MASAKI  慶應義塾大学, 医学部, 講師 (70296557)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
Keywords発生・分化 / 発現制御 / 遺伝子 / 循環器・高血圧 / 再生医学 / 発生分化
Outline of Final Research Achievements

Using the murine model, we identified that the expression of a neurovascular guiding molecule, Sema3C, is regulated positively by Foxc1 and Foxc2, and negatively by Tbx1 directly in the second heart field and through Fgf8 which is a downstream effector of Tbx1 in the neural crest, respectively, during development of the cardiac outflow tract. Such dynamic temporo-spatial regulation of Sema3c plays a role in the fine tuning of migration of neural crest cells into the outflow tract to give rise to the septum. We also succeeded in visualization of the development of pulmonary arteries from central to peripheral regions of the lungs using a transgenic mouse model in which the lacZ marker gene was inserted into the genome of IP3R type2. Using this mouse model, we also showed the mechanism of pulmonary vascular abnormality associated with cardiac outflow tract defects and candidates of unknown cis/trans elements that specifically regulate the development of pulmonary arterial smooth muscle.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (15 results)

All 2016 2015 2014 2013

All Journal Article (8 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (3 results) (of which Invited: 2 results) Book (4 results)

  • [Journal Article] Variable severity of cardiovascular phenotypes in patients with an early‑onset form of Marfan syndrome harboring FBN1 mutations in exons 24–322016

    • Author(s)
      Maeda J, Kosaki K, Shiono J, Kouno K, Aeba R, Yamagishi H
    • Journal Title

      Heart Vessels

      Volume: online 21 Jan Issue: 10 Pages: 1-7

    • DOI

      10.1007/s00380-016-0793-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pulmonary Arterial Hypertension Associated With Tetralogy of Fallot2015

    • Author(s)
      Yasuhara J, Yamagishi H
    • Journal Title

      International Heart Journal

      Volume: 56 Issue: Supplement Pages: S17-S21

    • DOI

      10.1536/ihj.14-351

    • NAID

      130004941325

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 【作用機序から考える薬物療法】 肺高血圧症2015

    • Author(s)
      小柳喬幸, 山岸敬幸
    • Journal Title

      小児科

      Volume: 56 Pages: 251-259

    • Related Report
      2015 Annual Research Report
  • [Journal Article] 【小児循環器診療のいま】 ピンポイント小児医療 心筋疾患 診断 肥大型心筋症と症候群2015

    • Author(s)
      石崎怜奈, 山岸敬幸
    • Journal Title

      小児内科

      Volume: 47 Pages: 214-219

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Myocardium-derived angiopoietin-1 is essential for coronary vein formation in the developing heart2014

    • Author(s)
      Arita Y, Nakaoka Y, Matsunaga T, Kidoya H, Yamamizu K, Arima Y, Kataoka-Hashimoto T, Ikeoka K, Yasui T, Masaki T, Yamamoto K, Higuchi K, Park JS, Shirai M, Nishiyama K, Yamagishi H, Otsu K, Kurihara H, Minami T, Yamauchi-Takihara K, Koh GY, Mochizuki N, Takakura N, Sakata Y, Yamashita JK, Komuro I
    • Journal Title

      Nat Commun

      Volume: 5 Issue: 1 Pages: 4452-4452

    • DOI

      10.1038/ncomms5552

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute rupture of chordae tendineae of the mitral valve in infants: a nationwide survey in Japan exploring a new syndrome.2014

    • Author(s)
      Shiraishi I, Nishimura K, Sakaguchi H, Abe T, Kitano M, Kurosaki K, Kato H, Nakanishi T, Yamagishi H, Sagawa K, Ikeda Y, Morisaki T, Hoashi T, Kagisaki K, Ichikawa H.
    • Journal Title

      Circulation

      Volume: 130 Issue: 13 Pages: 1053-1061

    • DOI

      10.1161/circulationaha.114.008592

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures.2014

    • Author(s)
      Mizuha Akiyama, Rie Wada, Kohei Inagawa, Takahiko Nishiyama, Ruri Kaneda, Toru Fukuda, Shu Takeda, Shugo Tohyama, Hisayuki Hashimoto, Yoshifumi Kawamura, Naoki Goshima, Ryo Aeba, Hiroyuki Yamagishi, Keiichi Fukuda, Masaki Ieda
    • Journal Title

      EMBO J.

      Volume: 33 Issue: 14 Pages: 1565-1581

    • DOI

      10.15252/embj.201387605

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Induction of human cardiomyocyte-like cells from fibroblasts by defined factors2013

    • Author(s)
      Wada R, Muraoka N, Inagawa K, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Kaneda R, Suzuki T, Kamiya K, Tohyama S, Yuasa S, Kokaji K, Aeba R, Yozu R, Yamagishi H, Kitamura T, Fukuda K, Ieda M
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 110 Pages: 12667-12672

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 先天性心疾患の診療をもっと面白くする臨床心臓発生学のすゝめ2015

    • Author(s)
      山岸敬幸
    • Organizer
      第33回中国四国地区小児循環器懇話会
    • Place of Presentation
      岡山国際交流センター(岡山県岡山市)
    • Year and Date
      2015-09-05
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] A history and interaction of outflow progenitor cells implicated in TAKAO syndrome.2013

    • Author(s)
      Hiroyuki Yamagishi
    • Organizer
      The 7th TAKAO International Symposium on Etiology and Morphogenesis of Congenital Heart Disease
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Understanding the developing mechanism of Truncus Arteriosus by Tbx1 hypomorphic mouse.2013

    • Author(s)
      Understanding the developing mechanism of Truncus Arteriosus by Tbx1 hypomorphic mouse. Takatoshi Tsuchihashi, Reina Ishizaki, Akimichi Shibata, Keiko Uchida, Hiroyuki Yamagishi
    • Organizer
      The 7th TAKAO International Symposium on Etiology and Morphogenesis of Congenital Heart Disease
    • Place of Presentation
      Tokyo
    • Related Report
      2013 Annual Research Report
  • [Book] Congenital Heart Disease The Broken Heart2016

    • Author(s)
      Yamagishi H
    • Total Pages
      765
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] Etiology and Morphogenesis of Congenital Heart Disease2016

    • Author(s)
      Yamagishi H, Kodo K, Maeda J, Uchida K, Tsuchihashi T, Shibata A, Ishizaki R, Yamagishi C, Srivastava D
    • Total Pages
      383
    • Publisher
      Springer
    • Related Report
      2015 Annual Research Report
  • [Book] Cardiac Regeneration Using Stem Cells2013

    • Author(s)
      Hiroyuki Yamagishi
    • Total Pages
      366
    • Publisher
      CRC Press
    • Related Report
      2013 Annual Research Report
  • [Book] Cardiac CT and MR for Adult Congenital Heart Disease2013

    • Author(s)
      Hiroyuki Yamagishi, Chihiro Yamagishi
    • Total Pages
      733
    • Publisher
      Springer
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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