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2013 Fiscal Year Final Research Report

Molecular mechanisms of ductus arteriosus closure

Research Project

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Project/Area Number 23390277
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionJikei University School of Medicine (2012-2013)
Waseda University (2011)

Principal Investigator

MINAMISAWA Susumu  東京慈恵会医科大学, 医学部, 教授 (40257332)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Utako  横浜市立大学, 医学部, 講師 (70404994)
GODA Nobuhito  早稲田大学, 理工学術院, 教授 (00245549)
Co-Investigator(Renkei-kenkyūsha) ISHIKAWA Yoshihiro  横浜市立大学, 横浜市立大学, 教授 (40305470)
NAKAMURA Tomoyuki  関西医科大学, 医学部, 教授 (20362527)
SUGIMOTO Yukihiko  熊本大学, 生命科学研究部, 教授 (80243038)
AOKI Hiroki  久留米大学, 循環器病研究所, 教授 (60322244)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsvascular remodeling / 動脈管 / 新生児 / 弾性線維 / プロスタグランジン / 酸素化
Research Abstract

The ductus arteriosus (DA) is an essential fetal artery that closes immediately after birth. However, the molecular mechanisms remain unknown, especially its vascular remodeling. We found that 1) prostaglandin E2 (PGE2) -EP4 signaling decreased elastic fiber formation through degradation of the cross-linking enzyme lysyl oxidase, and that 2) NFkB signal could be activated by PGE2-EP4 stimulation via cAMP-independent pathway, and that 3) endothelial cells of the DA exhibited a unique gene profile involved in the regulation of DA-specific morphology and function. These novel findings regarding DA vascular remodeling could open a possibility to innovate a new therapeutic strategy for the regulation of DA closure.

  • Research Products

    (17 results)

All 2014 2013 2012 2011 Other

All Journal Article (9 results) Presentation (5 results) Book (1 results) Remarks (2 results)

  • [Journal Article] Prostaglandin E2 inhibits elastogenesis in the ductus arteriosus via EP4 signaling2014

    • Author(s)
      Y okoyama U, Minamisawa S, Shioda A, Ishiwata R, Jin MH, Masuda M, Asou T, Sugimoto Y, Aoki H, Nakamura T, Ishikawa Y
    • Journal Title

      Circulation

      Volume: 129(4) Pages: 487-96

  • [Journal Article] Role of ion channels in ductus arteriosus closure2014

    • Author(s)
      Minamisawa S, Akaike T
    • Journal Title

      Human Genetics & Embryology : Current Research

      Volume: 3 Pages: 116

    • DOI

      10.4172/2161-0436.1000116

  • [Journal Article] Thromboxane A2 receptor stimulation promotes closure of the rat ductus arteriosus through enhancing neointima formation2014

    • Author(s)
      Yokota T, Shiraishi R, Aida T, Iwai K, Liu NM, Y okoyama U, Minamisawa S
    • Journal Title

      PLoS One

      Volume: 9(4) Pages: e94895

  • [Journal Article] Transcription profiles of the ductus arteriosus in Brown-Norway rat with irregular elastic fiber formation2014

    • Author(s)
      Hsieh YT, Liu NM, Ohmori E, Y okota T, Kajimura I, Akaike T, Ohshima T, Goda N, Minamisawa S
    • Journal Title

      Circ J

      Volume: 8(5) Pages: 1224-33

  • [Journal Article] Transcription Profiles of Endothelial Cells in the Rat Ductus Arteriosus during a Perinatal Period2013

    • Author(s)
      Liu NM, Yokota T, Maekawa S, Lü P, Tei I, Taniguchi H, Yokoyama U, Kato T, Minamisawa S
    • Journal Title

      PLoS One

      Volume: 8(9) Pages: e73685

  • [Journal Article] 酸素化によるラット動脈管平滑筋細胞からのエラスチン分泌の減少2013

    • Author(s)
      川上翔士, 南沢享
    • Journal Title

      日本小児循環器学会雑誌

      Volume: 29(6) Pages: 309-315

  • [Journal Article] Inhibition of EP4 signaling attenuates aortic aneurysm formation2012

    • Author(s)
      Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, Ichikawa Y, Kumagaya S, Katayama Y, Fujita T, Okumura S, Sato M, Sugimoto Y, Aoki H, Suzuki S, Masuda M, Minamisawa S, Ishikawa Y
    • Journal Title

      PLoS One

      Volume: 7(5) Pages: e36724

  • [Journal Article] Low-dose thromboxane A2 receptor stimulation promotes closure of the rat ductus arteriosus with minimal adverse effects2012

    • Author(s)
      Yokota T, Aida T, Ichikawa Y, Fujita T, Yokoyama U, Minamisawa S
    • Journal Title

      Pediatr Res

      Volume: 72(2) Pages: 129-36

  • [Journal Article] DNA microarray profiling identified a new role of growth hormone in vascular remodeling of rat ductus arteriosus2011

    • Author(s)
      Jin MH, Y okoyama U, Sato Y, Shioda A, Jiao Q, Ishikawa Y, Minamisawa S
    • Journal Title

      J Physiol Sci

      Volume: 61(3) Pages: 167-79

  • [Presentation] Prostaglandin Eシグナルによるlysyl oxidase分解亢進が動脈管弾性線維の形成不良を引き起こす2013

    • Author(s)
      南沢享, 横山詩子, 青木浩樹, 中邨智之, 石川義弘
    • Organizer
      生理学研究所研究会「心血管膜輸送分子の構造・機能・病態の統合的研究戦略」
    • Place of Presentation
      岡崎, 生理学研究所1階大会議室
    • Year and Date
      20131127-28
  • [Presentation] cAMP medication for cardiovascular diseases2013

    • Author(s)
      Minamisawa S (シンポジスト), Y okoyaman U, Ishikawa Y
    • Organizer
      The 90th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Tokyo
    • Year and Date
      20130327-29
  • [Presentation] Prostaglandin E2-EP4 Signaling Inhibits V ascular Elastic Fiber Formation in the Rodent Ductus Arteriosus2012

    • Author(s)
      Minamisawa S, Y okoyama U, Ishiwata R, Sugimoto Y , Aoki H, Nakamura T , Ishikawa Y
    • Organizer
      2012 the American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco, California
    • Year and Date
      20121215-19
  • [Presentation] The endothelial cells of ductus arteriosus have a unique gene profile to control vascular morphology2011

    • Author(s)
      Liu N, Yokota T , Maekawa S, Yokoyama U, Kato T , Minamisawa S
    • Organizer
      Experimental Biology 2012
    • Place of Presentation
      San Diego
    • Year and Date
      20111000
  • [Presentation] A comprehensive approach to understand the formation of the cardiovascular network (Overview)2011

    • Author(s)
      Minamisawa S(シンポジスト)
    • Organizer
      The 88th Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Yokohama
    • Year and Date
      20110328-30
  • [Book] Recent advances concerning the molecular mechanism of patent ductus arteriosus. In: P . Syamasundar Rao (ed). Congenital Heart disease-Selected Aspects2012

    • Author(s)
      Minamisawa S, Yokoyama U
    • Total Pages
      85-96
    • Publisher
      InTech - Open Access Publisher
  • [Remarks] 東京慈恵会医科大学 細胞生理学講座ホームページ

    • URL

      http://sminamis.m38.coreserver.jp/Jikei_Cell_Physiology/Welcome.html

  • [Remarks] アウトリーチ活動早稲田大学理工学術院主催のユニラブにて, 2010年, 2011年に小学生向けの心臓血管教室を開催した.

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Published: 2015-06-25   Modified: 2021-06-07  

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