Molecular mechanisms of remodeling of the ductus arteriosus

• Project/Area Number: 16H05358
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pediatrics
• Research Institution: Yokohama City University
• Principal Investigator: Yokoyama Utako 横浜市立大学, 医学部, 准教授 (70404994)
• Co-Investigator(Kenkyū-buntansha): 藤田 秀次郎 横浜市立大学, 医学研究科, 共同研究員 (90381516)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 動脈管 / 発生・分化 / 生理学 / シグナル伝達 / リモデリング

Outline of Final Research Achievements

The ductus arteriosus (DA) closes after birth to adapt to the robust changes in hemodynamics, which require intimal thickening to occur. The tissue-type plasminogen activator (t-PA) mRNA expression level was higher in DA endothelial cells (ECs) than in aortic ECs. t-PA-mediated marked gelatinase activity was observed at the site of disruption in the internal elastic laminae (IEL). In vivo administration of plasminogen to pre-term rat fetuses, in which intimal thickening is poorly formed, promoted IEL disruption accompanied by gelatinase activation, and enhanced intimal thickening formation in the DA. We also identified Fbln1 as a candidate gene for intimal thickening. Fibulin-1 is induced via plostaglandineE-EP4receptor signaling pathway in DA smooth muscle cells (SMCs). Fibulin-1 promoted SMC migration in combination with fibulin-1 binding protein versican. In conclusions, EC-derived t-PA and SMC-derived fibulin-1 promoted DA intimal thickening.

Academic Significance and Societal Importance of the Research Achievements

胎児期に存在する動脈管は出生後には速やかに閉鎖するが、早産児では出生後の動脈管開存症が生命予後を悪化させ、ある種の先天性心疾患では出生後にも動脈管の開存が必要である。つまり、動脈管の閉鎖と開存の制御は小児医療上極めて重要な課題である。動脈管の完全な閉鎖には、胎生中期から始まる解剖学的リモデリングである内膜肥厚が重要な役割を果たす。しかしながら現在の治療では内膜肥厚形成を制御することができておらず、十分な効果が得られていない。本研究から内膜肥厚における内弾性板断裂から平滑筋細胞の遊走の分子機序が明らかとなった。これら分子を生体内で誘導することができれば動脈管の制御につながる可能性がある。

Research Products

• [Journal Article] Antenatal Administration of Betamethasone Contributes to Intimal Thickening of the Rat Ductus Arteriosus (2019)
  • Author(s): Kemmotsu T., Yokoyama U., Saito J., Ito S., Uozumi A., Nishimaki S., Iwasaki S., Seki K., Ito S., Ishikawa Y
  • Journal Title: Circulation Journal Volume: 83 Issue: 3 Pages: 654-661
  • DOI: 10.1253/circj.CJ-18-1033
  • NAID: 130007604194
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-02-25
  • Peer Reviewed / Open Access
• [Journal Article] Usefulness of Exchanged Protein Directly Activated by cAMP (Epac)1-Inhibiting Therapy for Prevention of Atrial and Ventricular Arrhythmias in Mice (2019)
  • Author(s): Prajapati R, Fujita T, Suita K, Nakamura T, Cai W, Hidaka Y, Umemura M, Yokoyama U, Knollmann BC, Okumura S, Ishikawa Y
  • Journal Title: Circulation Journal Volume: 83 Issue: 2 Pages: 295-303
  • DOI: 10.1253/circj.CJ-18-0743
  • NAID: 130007557004
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-01-25
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Epac1 deficiency inhibits basic fibroblast growth factor-mediated vascular smooth muscle cell migration (2019)
  • Author(s): Yuko Kato, Utako Yokoyama, Takayuki Fujita, Masanari Umemura, Tetsuo Kubota, Yoshihiro Ishikawa
  • Journal Title: The Journal of Physiological Sciences Volume: 69 Issue: 2 Pages: 175-184
  • DOI: 10.1007/s12576-018-0631-7
  • NAID: 40021818894
  • Peer Reviewed / Open Access
• [Journal Article] An appropriately sized soft polyester external stent prevents enlargement and neointimal hyperplasia of a saphenous vein graft in a canine model (2019)
  • Author(s): Yasuda Shota、Goda Motohiko、Shibuya Taisuke、Uchida Keiji、Suzuki Shinichi、Noishiki Yasuharu、Yokoyama Utako、Ishikawa Yoshihiro、Masuda Munetaka
  • Journal Title: Artificial Organs Volume: 印刷中 Issue: 6 Pages: 577-583
  • DOI: 10.1111/aor.13399
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous hyperthermia-chemotherapy effect by arterial injection of Fe(Salen) for femur tumor (2018)
  • Author(s): Umemura Masanari、Islam Md. Rafikul、Fukumura Hidenobu、Sato Itaru、Kawabata Yusuke、Matsuo Kousuke、Nakakaji Rina、Nagasako Akane、Ohtake Makoto、Takayuki Fujita、Yokoyama Utako、Nakayama Tomohiro、Eguchi Haruki、Ishikawa Yoshihiro
  • Journal Title: Cancer Science Volume: 110 Issue: 1 Pages: 356-365
  • DOI: 10.1111/cas.13851
  • Peer Reviewed / Open Access
• [Journal Article] 動脈管閉鎖におけるt-PA活性の役割 (2018)
  • Author(s): 横山詩子, 齋藤純一, 石川義弘
  • Journal Title: 日本血栓止血学会誌 Volume: 29
• [Journal Article] Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal (2018)
  • Author(s): Yokoyama U, Arakawa N, Ishiwata R, Yasuda S, Minami T, Goda M, Uchida K, Suzuki S, Matsumoto M, Koizumi N, Taguri M, Hirano H, Yoshimura K, Ogino H, Masuda M, Ishikawa Y.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 315 Issue: 4 Pages: H1012-H1018
  • DOI: 10.1152/ajpheart.00329.2018
  • Peer Reviewed / Open Access
• [Journal Article] Hydrostatic pressure suppressed fibrotic change via Akt/GSK-3 signaling in human cardiac fibroblasts. (2018)
  • Author(s): Tanaka R, Umemura M, Narikawa M, Fujita T, Yokoyama U, Ishigami T, Kimura K, Tamura K, Ishikawa Y.
  • Journal Title: Physiol Rep. Volume: 6 Issue: 9 Pages: e13687-e13687
  • DOI: 10.14814/phy2.13687
  • Peer Reviewed / Open Access
• [Journal Article] Vidarabine, an anti-herpesvirus agent, prevents catecholamine-induced arrhythmias without adverse effect on heart function in mice (2018)
  • Author(s): Suita Kenji、Fujita Takayuki、Cai Wenqian、Hidaka Yuko、Jin Huiling、Prajapati Rajesh、Umemura Masanari、Yokoyama Utako、Sato Motohiko、Knollmann Bj?rn C.、Okumura Satoshi、Ishikawa Yoshihiro
  • Journal Title: Pfl?gers Archiv - European Journal of Physiology Volume: 未定 Issue: 6 Pages: 923-935
  • DOI: 10.1007/s00424-018-2121-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Acute hyperthermia inhibits TGF-β1-induced cardiac fibroblast activation via uppression of Akt Signaling. (2018)
  • Author(s): Narikawa M, Umemura M, Tanaka R, Fujita T, Yokoyama U, Ishigami T, Kimura K, Tamura K, Ishikawa Y.
  • Journal Title: Sci Rep. Volume: 8 Issue: 1 Pages: 6277-6277
  • DOI: 10.1038/s41598-018-24749-6
  • Peer Reviewed / Open Access
• [Journal Article] Fabrication of engineered tubular tissue for small blood vessels via three-dimensional cellular assembly and organization ex vivo (2018)
  • Author(s): Masuda T, Ukiki M, Yamagishi Y, Matsusaki M, Akashi M, Yokoyama U, and Arai F
  • Journal Title: J Biotechnol Volume: 20 Pages: 46-53
  • DOI: 10.1016/j.jbiotec.2018.04.003
  • Peer Reviewed / Open Access
• [Journal Article] A selective antagonist of prostaglandin E receptor subtype 4 attenuates abdominal aortic aneurysm. (2018)
  • Author(s): Mamun A, Yokoyama U, Saito J, Ito S, Hiromi T, Umemura M, Fujita T, Yasuda S, Minami T, Goda M, Uchida K, Suzuki S, Masuda M, Ishikawa Y.
  • Journal Title: Physiol Rep. Volume: 6 Issue: 18
  • DOI: 10.14814/phy2.13878
  • Peer Reviewed / Open Access
• [Journal Article] Alternating magnetic field (AMF) enhances cytotoxicity of compound c. (2018)
  • Author(s): Akimoto T, Umemura M, Nagasako A, Ohtake M, Fujita T, Yokoyama U, Eguchi H, Yamamoto T, Ishikawa Y.
  • Journal Title: Cancer Sci. Volume: 109 Issue: 11 Pages: 3483-3493
  • DOI: 10.1111/cas.13781
  • Peer Reviewed / Open Access
• [Journal Article] Treatment of oral cancer using magnetized paclitaxel (2018)
  • Author(s): Nakakaji Rina、Umemura Masanari、Mitsudo Kenji、Kim Jeong-Hwan、Hoshino Yujiro、Sato Itaru、Masuda Takatsugu、Yamamoto Masahiro、Kioi Mitomu、Koizumi Toshiyuki、Fujita Takayuki、Yokoyama Utako、Iida Masaki、Sato Motohiko、以下7名
  • Journal Title: Oncotarget Volume: 9 Issue: 21 Pages: 15591-15605
  • DOI: 10.18632/oncotarget.24570
  • Peer Reviewed / Open Access
• [Journal Article] The iron chelating agent, deferoxamine detoxifies Fe(Salen)-induced cytotoxicity (2017)
  • Author(s): Umemura Masanari、Kim Jeong-Hwan、Aoyama Haruki、Hoshino Yujiro、Fukumura Hidenobu、Nakakaji Rina、Sato Itaru、Ohtake Makoto、Akimoto Taisuke、Narikawa Masatoshi、Tanaka Ryo、Fujita Takayuki、Yokoyama Utako、Taguri Masataka、Okumura Satoshi、Sato Motohiko、Eguchi Haruki、Ishikawa Yoshihiro
  • Journal Title: Journal of Pharmacological Sciences Volume: 134 Issue: 4 Pages: 203-210
  • DOI: 10.1016/j.jphs.2017.07.002
  • Peer Reviewed / Open Access
• [Journal Article] L-DOPA sensitizes vasomotor tone by modulating the vascular alpha1-adrenergic receptor (2017)
  • Author(s): Masukawa Daiki、Koga Motokazu、Sezaki Anna、Nakao Yuka、Kamikubo Yuji、Hashimoto Tatsuo、Okuyama-Oki Yuki、Aladeokin Aderemi Caleb、Nakamura Fumio、Yokoyama Utako、Wakui Hiromichi、Ichinose Hiroshi、Sakurai Takashi、Umemura Satoshi、Tamura Koichi、Ishikawa Yoshihiro、Goshima Yoshio
  • Journal Title: JCI Insight Volume: 2 Issue: 18 Pages: 1-16
  • DOI: 10.1172/jci.insight.90903
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cardiac overexpression of Epac1 in transgenic mice rescues lipopolysaccharide-induced cardiac dysfunction and inhibits Jak-STAT pathway. (2017)
  • Author(s): Huiling Jin, Takayuki Fujita, Meihua Jin, Reiko Kurotani, Iyuki Namekata, Shogo Hamaguchi, Yuko Hidaka, Wenqian Cai, Kenji Suita, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Rajesh Prajapati, Chen Liang, Masanari Umemura, Utako Yokoyama, Motohiko Sato, Hikaru Tanaka, Satoshi Okumura, Yoshihiro Ishikawa.
  • Journal Title: J Mol Cell Cardiol. Volume: 108 Pages: 170-180
  • DOI: 10.1016/j.yjmcc.2017.05.014
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Attenuation of ductus arteriosus intimal thickening in preterm sheep twins compared with singletons (2017)
  • Author(s): Ito Satoko、Yokoyama Utako、Saito Junichi、Sato Shinichi、Usuda Haruo、Watanabe Shimpei、Kitanishi Ryuta、Miura Yuichiro、Saito Masatoshi、Hanita Takushi、Matsuda Tadashi、Ishikawa Yoshihiro
  • Journal Title: The Journal of Physiological Sciences Volume: 67 Issue: 6 Pages: 723-729
  • DOI: 10.1007/s12576-017-0565-5
  • NAID: 40021363517
  • Peer Reviewed / Open Access
• [Journal Article] Pathology and Molecular Mechanisms of Coarctation of the Aorta and its Association with the Ductus Arteriosus. (2017)
  • Author(s): Yokoyama U, Ichikawa Y, Minamisawa S, Ishikawa Y
  • Journal Title: J Physiol Sci. Volume: 67 Issue: 2 Pages: 259-270
  • DOI: 10.1007/s12576-016-0512-x
  • NAID: 40021113914
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced EP4 Expression in a Pulmonary Artery Aneurysm With Dissection in a Patient With Pulmonary Arterial Hypertension (2017)
  • Author(s): S. Akagi, K. Nakamura, U. Yokoyama, S. Kasahara, T. Sarashina, K. Ejiri, H. Ito
  • Journal Title: Circulation: Cardiovascular Imaging Volume: 10 Issue: 2
  • DOI: 10.1161/circimaging.116.005839
  • Peer Reviewed / Open Access
• [Journal Article] Arterial graft with elastic layer structure grown from cells. (2017)
  • Author(s): Yokoyama U, Tonooka Y, Koretake R, Akimoto T, Gonda Y, Saito J, Umemura M, Fujita T, Sakuma S, Arai F, Kaneko M, Ishikawa Y.
  • Journal Title: Sci Rep Volume: 1 Issue: 1 Pages: 140-140
  • DOI: 10.1038/s41598-017-00237-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Epac activation inhibits IL-6-induced cardiac myocyte dysfunction. (2016)
  • Author(s): Jin H，Fujita T，Jin M，Kurotani R，Hidaka Y，Cai W，Suita K，Prajapati R，Liang C，Ohnuki Y，Mototani Y，Umemura M，Yokoyama U，Sato M，Okumura S，Ishikawa Y.
  • Journal Title: J Physiol Sci. Volume: 印刷中 Issue: 1 Pages: 77-87
  • DOI: 10.1007/s12576-016-0509-5
  • NAID: 40021443658
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Transient receptor potential cation 3 channel regulates melanoma proliferation and migration． (2016)
  • Author(s): Oda K，Umemura M，Nakakaji R，Tanaka R，Sato I，Nagasako A，Oyamada C，Baljinnyam E，Katsumata M，Xie L，Narikawa M，Yamaguchi Y，Akimoto T，Ohtake M，Fujita T，Yokoyama U，Iwatsubo K，Aihara M and Ishikawa Y
  • Journal Title: J Physiol Sci. Volume: 該当なし Issue: 4 Pages: 497-505
  • DOI: 10.1007/s12576-016-0480-1
  • NAID: 40021238419
  • Peer Reviewed / Open Access
• [Journal Article] Glutamate promotes contraction of the rat ductus arteriosus. (2016)
  • Author(s): Fujita S, Yokoyama U, Ishiwata R, Aoki R, Nagao K, Masukawa D, Umemura M, Fujita T, Iwasaki S, Nishimaki S, Seki K, Ito S, Goshima Y, Asou T, Masuda M, Ishikawa Y.
  • Journal Title: Circ J Volume: 80 Pages: 2388-2396
  • NAID: 130005433144
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Gaseous components of cigarette smoke upregulate prostaglandin E2 receptor EP4 in aortic aneurysm (2019)
  • Author(s): Hiromi T, Yokoyama U, Takeuchi I, and Ishikawa Y
  • Organizer: The 9th Federation of the Asian and Oceanian Physiological Societies Congress
  • Int'l Joint Research / Invited
• [Presentation] へその緒から作る人工血管 心臓病の子供たちに成長する人工血管を届けたい (2019)
  • Author(s): 齋藤純一、横山詩子
  • Organizer: 市民講座「細胞エクササイズで頑丈な人工血管を作ろう！」
  • Invited
• [Presentation] 細胞をトレーニングしたら頑丈な血管ができた！細胞から血管を作る加圧トレーニングのレシピを発見 (2019)
  • Author(s): 横山詩子
  • Organizer: 市民講座「細胞エクササイズで頑丈な人工血管を作ろう！」
  • Invited
• [Presentation] 動脈管は面白い！100年前からの謎を解く (2019)
  • Author(s): 横山詩子
  • Organizer: 横浜市立大学小児科リサーチ発表会
  • Invited
• [Presentation] 動脈管の内皮細胞による血管リモデリング (2019)
  • Author(s): 齋藤純一 and 横山詩子
  • Organizer: 第13回 新生児科指導医教育セミナー
  • Invited
• [Presentation] 静水圧印加による血管系組織の再生 (2018)
  • Author(s): 横山詩子
  • Organizer: 都医学研セミナー
  • Invited
• [Presentation] How ”Human arterial graft” should be fabricated? (2018)
  • Author(s): Yokoyama U
  • Organizer: CBS 2018- IEEE International Conference on Cyborg and Bionic Systems
  • Int'l Joint Research / Invited
• [Presentation] 動脈管作動薬の作用機序ー薬物療法の基礎として (2018)
  • Author(s): 横山詩子
  • Organizer: 第10回教育セミナー Advanced Course 主催：日本小児循環器学会学術委員会・教育委員会
  • Invited
• [Presentation] 三次元血管モデルの有用性 (2018)
  • Author(s): 横山詩子
  • Organizer: オープンイノベーションカンファレンスIII
  • Invited
• [Presentation] 動脈管閉鎖における内皮機能の役割 (2018)
  • Author(s): 齋藤純一、横山詩子、益田宗孝、麻生俊英、石川義弘
  • Organizer: 第54回日本小児循環器学会総会・学術集会
  • Invited
• [Presentation] 肺高血圧に合併した肺動脈瘤におけるEP4 の発現とその意義 (2018)
  • Author(s): 赤木達、中村一文、横山詩子、笠原真悟、更科俊洋、江尻健太郎、伊藤浩
  • Organizer: 第3回日本肺高血圧・肺循環学会学術集会
  • Invited
• [Presentation] 周期加圧培養法による人工血管の作成 (2018)
  • Author(s): 石川義弘、横山詩子、齋藤純一、金子真
  • Organizer: 第39回日本循環制御医学会総会
  • Invited
• [Presentation] 周期的加圧培養による移植可能な血管グラフトの作製 (2018)
  • Author(s): 齋藤純一、横山詩子、高山俊男、洞出光洋、伊藤弘明、須郷慶信、倉澤健太郎、宮城悦子、金子真、石川義弘
  • Organizer: 第17回日本心臓血管発生研究会
• [Presentation] 母体ラットへのべタメタゾン投与が動脈管内膜肥厚に与える作用の検討 (2018)
  • Author(s): 釼持孝博、横山詩子、齋藤純一、伊藤智子、魚住梓、岩崎志穂、西巻滋、関和男、伊藤秀一、石川義弘
  • Organizer: 第63回日本新生児成育医学科医・学術集会
• [Presentation] プロスタグランディンE-EP4シグナルによる大動脈瘤進行の分子機序 (2018)
  • Author(s): 横山詩子, 廣見太郎, and 石川義弘
  • Organizer: 心血管膜輸送研究会2018
• [Presentation] Mechanoresponse to periodic hydrostatic pressure enables fabrication of human arterial graft (2018)
  • Author(s): Saito J, Yokoyama U, Takayama T, Horade M, Ito H, Sugo Y, Kurasawa K, Ogawa M, Miyagi E, Kaneko M, and Ishikawa Y
  • Organizer: American Society for Matrix Biology Biennial Meeting 2018
  • Int'l Joint Research
• [Presentation] プロスタグランディンE受容体EP4シグナルは腹部大動脈瘤の増悪に関与する (2018)
  • Author(s): 廣見太郎, 横山詩子, Al M, 竹内一郎, and 石川義弘
  • Organizer: CCM輸液・栄養研究会
• [Presentation] Prostaglandin E2 promotes vascular remodeling of the ductus arteriosus (2018)
  • Author(s): Minamisawa S, Akaike T, and Yokoyama U
  • Organizer: The 25th Euro Congress on Pediatric Heart Disease and Health
  • Int'l Joint Research
• [Presentation] Fibulin-1の動脈管内膜肥厚形成における役割 (2018)
  • Author(s): 中川路太一、横山詩子、伊藤智子、石川義弘
  • Organizer: 第28回日本病態生理学会大会
• [Presentation] 胎盤由来プロスタグランディンEはFibulin-1を介した動脈管リモデリングを促進する (2018)
  • Author(s): 横山詩子、伊藤智子、石川義弘
  • Organizer: 第50回日本結合組織学会学術大会
• [Presentation] Tissue-type plasminogen activator promotes intimal thickening formation of the ductus arteriosus (2018)
  • Author(s): Saito J, Yokoyama U, Nicho N, Zheng YW, Ito S, Ito S, Taniguchi H, Asou T, Masuda M, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Presentation] Antenatal administration of betamethasone promotes closure of the preterm ductus arteriosus via intimal thickening formation (2018)
  • Author(s): Kemmotsu T, Yokoyama U, Azuma S, Saito J, Ito S, Uozumi A, Nishimaki S, Iwasaki S, Seki K, Ito S, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Presentation] Prostaglandin E-EP4 signaling-mediated fibulin-1 integrates extracellular matrices to promote smooth muscle cell migration of the ductus arteriosus (2018)
  • Author(s): Ito S, Yokoyama U, Saito JZ, Y.W., Masuda M, Asou T, and Ishikawa Y
  • Organizer: Weinstein 2018 Cardiovascular Development and Regeneration Conference
  • Int'l Joint Research
• [Presentation] Fabrication of scaffold-free human vascular graft by periodic hydrostatic pressurization. (2018)
  • Author(s): Yokoyama, U., Saito, J., Ito, H., Tadokoro, T., Taniguchi, H., Kaneko, M. Ishikawa, Y.
  • Organizer: The 95th Annual Meeting of the Physiological Society of Japan
  • Invited
• [Presentation] 肺血管の発達と密接な関連を有する動脈管の発達 (2018)
  • Author(s): 横山詩子
  • Organizer: 第２４回日本小児肺循環研究会
  • Invited
• [Presentation] Tissue-type plasminogen activator contributes to remodeling of the ductus arteriosus. (2018)
  • Author(s): Saito, J., Yokoyama, U. Ishikawa, Y.
  • Organizer: The 95th Annual Meeting of the Physiological Society of Japan
• [Presentation] Epac1 deficiency inhibits bFGF-induced neointimal formation via diminished phosphorylation of GSK3beta. (2018)
  • Author(s): Kato, Y., Yokoyama, U., Fujita, T., Kubota, T. Ishikawa, Y.
  • Organizer: The 95th Annual Meeting of the Physiological Society of Japan
• [Presentation] Oxygenation-induced postnatal remodeling of the ductus arteriosus. (2017)
  • Author(s): Jin MH, Yokoyama U, Ishiwata R, Minamisawa S, Ishikawa Y.
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 浜松アクトシティコングレスセンター（静岡県浜松市）
  • Year and Date: 2017-03-28
  • Invited
• [Presentation] Human gene analysis identified tissue plasminogen activator as a mediator of disrupting the internal elastic lamina in the ductus arteriosus. (2017)
  • Author(s): Saito J, Yokoyama U, Ishikawa Y.
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 浜松アクトシティコングレスセンター（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] An EP4 antagonist has inhibitory and therapeutic effects on mouse models of abdominal aortic aneurysm. (2017)
  • Author(s): Al Mamun, Yokoyama U, Ishiwata R, Isono O, Nagabukuro H, Ishikawa Y.
  • Organizer: The 94th Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: 浜松アクトシティコングレスセンター（静岡県浜松市）
  • Year and Date: 2017-03-28
• [Presentation] Clinical Course of Pulmonary Artery Aneurysm in Pulmonary Hypertension: Insight into Medical Treatment and Histological Characteristics (2017)
  • Author(s): Akagi S, Nakamura K, Yokoyama U, Sarashina T, Ejiri K, Itoh H.
  • Organizer: The 81th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: 石川県立音楽堂（石川県金沢市）
  • Year and Date: 2017-03-17
• [Presentation] Molecular mechanisms of the ductus arteriosus (2017)
  • Author(s): Yokoyama, U
  • Organizer: he 90th Scientific Session, American Heart Association
  • Int'l Joint Research / Invited
• [Presentation] New insights on how to treat patent ductus arteriosus. (2017)
  • Author(s): Yokoyama, U
  • Organizer: The 8th TAKAO International symposium
  • Int'l Joint Research / Invited
• [Presentation] プロスタグランディンE受容体EP4による弾性線維形成と破壊のメカニズム. (2017)
  • Author(s): 横山詩子、石渡遼、石川義弘.
  • Organizer: 第４９回日本結合組織学会
  • Invited
• [Presentation] 動脈管の基礎研究から臨床へ (2017)
  • Author(s): 横山詩子、南沢享、石川義弘.
  • Organizer: 第120回日本小児科学会学術集会
  • Invited
• [Presentation] プロスタグランディンE受容体EP4による血管の分化と破壊のメカニズム (2017)
  • Author(s): 横山詩子
  • Organizer: 横浜市立大学生命医科学研究科連携セミナー
  • Invited
• [Presentation] 知っておきたい大動脈瘤の進行のしくみ～世界初の治療薬開発に向けて～ (2017)
  • Author(s): 横山詩子
  • Organizer: 第49回先端医科学研究センター市民講座
  • Invited
• [Presentation] Fabrication of Implantable Human Arterial Graft by Periodic Hydrostatic Pressure (2017)
  • Author(s): Saito, J., Yokoyama, U., Ito, H., Tadokoro, T., Sugo, Y., Kurasawa, K., Ogawa, M., Miyagi, E., Taniguchi, H., Kaneko, M. Ishikawa, Y.
  • Organizer: The 8th TAKAO International symposium
  • Int'l Joint Research
• [Presentation] Antenatal Administration of Betamethasone Contributes to Intimal thickening of the Ductus Arteriosus. (2017)
  • Author(s): Kemmotsu, T., Yokoyama, U., Azuma, S., Saito, J., Ito, S., Uozumi, A., Iwasaki, S., Nishimaki, S., Ito, S., Masuda, M., Asou, T.Ishikawa, Y.
  • Organizer: The 8th TAKAO International symposium
  • Int'l Joint Research
• [Presentation] Prostaglandin E-EP4-mediated fibulin-1 up-regulation plays a role in intimal thickening of the ductus arteriosus. (2017)
  • Author(s): Ito, S., Yokoyama, U., Saito, J., Masuda, M., Asou, T.Ishikawa, Y.
  • Organizer: The 8th TAKAO International symposium
  • Int'l Joint Research
• [Presentation] 母体ラットへのベタメタゾン投与が動脈管閉鎖に与える作用の検討 (2017)
  • Author(s): 釼持孝博、横山詩子、齋藤純一、魚住梓、岩崎志穂、西巻滋、伊藤秀一、石川義弘.
  • Organizer: 第53回日本周産期・新生児医学会学術集会
• [Presentation] Fibulin-1 の動脈管内膜肥厚形成機序 (2017)
  • Author(s): 伊藤智子、横山詩子、石川義弘.
  • Organizer: 第53回日本周産期・新生児医学会学術集会
• [Presentation] 多胎妊娠では動脈管内膜肥厚が抑制される (2017)
  • Author(s): 伊藤智子、横山詩子、齋藤純一、佐藤信一、臼田治夫、渡邊真平、北西龍太、三浦雄一郎、埴田卓志、松田直、石川義弘.
  • Organizer: 第62回日本新生児成育医学会学術集会
• [Presentation] Fibulin-1 は平滑筋細胞遊走を介して動脈管内膜肥厚を誘導する (2016)
  • Author(s): 伊藤智子, 横山詩子, 益田宗孝, 麻生俊英, 石川義弘
  • Organizer: 第６１回日本新生児成育医学会学術集会
  • Place of Presentation: 大阪国際会議場（大阪府大阪市）
  • Year and Date: 2016-12-01
• [Presentation] EP4 signaling in smooth muscle cells attracts inflammatory immune responses in the aorta. (2016)
  • Author(s): Ishiwata R, Yokoyama U, Ichikawa Y, Kurotaki D, Yasuda S, Goda M, Suzuki S, Masuda M, Tamura T, Ishikawa Y.
  • Organizer: The 89th Scientific Session, American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Human Gene Profiling Reveals contribution of Tissue Plasminogen Activator to Intimal Thickening of the Ductus Arteriosus. (2016)
  • Author(s): Saito J, Yokoyama U, Masuda M, Asou T, Ishikawa Y.
  • Organizer: The 89th Scientific Session, American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] Fibulin-1 plays a role in smooth muscle cell migration and intimal thickening in the ductus arteriosus. (2016)
  • Author(s): Ito S, Yokoyama U, Yanai C, Masuda M, Asou T, Ishikawa Y.
  • Organizer: The 89th Scientific Session, American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] 組織型プラスミノーゲン活性化因子による動脈管内弾性板の分解 (2016)
  • Author(s): 齋藤純一, 横山詩子, 石川義弘
  • Organizer: 第15回日本心臓血管発生研究会
  • Place of Presentation: 国立循環器病研究センター（大阪府吹田市）
  • Year and Date: 2016-10-14
• [Presentation] PGE2-EP4シグナルはfibulin-1を介して動脈管平滑筋遊走を促進する (2016)
  • Author(s): 伊藤智子, 横山詩子, 石川義弘
  • Organizer: 第15回日本心臓血管発生研究会
  • Place of Presentation: 国立循環器病研究センター（大阪府吹田市）
  • Year and Date: 2016-10-14
• [Presentation] ヒト動脈管における内膜肥厚部の遺伝子プロファイリング (2016)
  • Author(s): 齋藤純一，横山詩子，麻生俊英，石川義弘
  • Organizer: 第52回日本周産期・新生児医学会学術集会
  • Place of Presentation: 富山国際会議場（富山県富山市）
  • Year and Date: 2016-07-16
• [Presentation] 平滑筋細胞におけるPGE2-EP4シグナルは腹部大動脈瘤の発症を促す (2016)
  • Author(s): 石渡 遼, 横山 詩子, 市川 泰弘, 黒滝 大翼, 田村 智彦, 石川 義弘
  • Organizer: 第３７回日本循環制御医学会総会
  • Place of Presentation: ステーションコンファレンス東京（東京都）
  • Year and Date: 2016-07-08
• [Presentation] 動脈硬化性疾患に対する薬物治療の開発 (2016)
  • Author(s): 横山詩子
  • Organizer: Atherosclerosis and Angiogenesis Research Frontier
  • Place of Presentation: 旭川グランドホテル（北海道旭川市）
  • Invited
• [Book] 小児・成育循環器学. 動脈管作用薬 (2018)
  • Author(s): 横山詩子
  • Total Pages: 724
  • Publisher: 診断と治療社
  • ISBN: 9784787822888
• [Book] ガイトン生理学 原著第13 版 第１４章：循環の概要；圧，流量，抵抗の生物物理学 (2018)
  • Author(s): 横山詩子
  • Total Pages: 1100
  • Publisher: エルゼビア・ジャパン社
• [Book] ガイトン生理学 原著第13 版 第１５章：動脈系と静脈系の血管伸展性と機能 (2018)
  • Author(s): 横山詩子
  • Total Pages: 1100
  • Publisher: エルゼビア・ジャパン社
• [Book] ガイトン生理学 原著第13 版 第８４章：胎児と新生児の生理学 (2018)
  • Author(s): 横山詩子、齋藤純一
  • Total Pages: 1100
  • Publisher: エルゼビア・ジャパン社
• [Book] 新版 先天性心疾患を理解するための臨床心臓発生学 動脈管閉鎖の分子機構 (2018)
  • Author(s): 横山詩子、南沢享
  • Publisher: メジカルビュー社
• [Book] 新版 先天性心疾患を理解するための臨床心臓発生学 動脈管開存症 (2018)
  • Author(s): 横山詩子、南沢享
  • Publisher: メジカルビュー社
• [Book] 小児循環器学 動脈管作用薬 (2018)
  • Author(s): 横山詩子
  • Publisher: 診断と治療社
• [Remarks] 横浜市立大学医学部循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/index.html
• [Remarks] 横浜市立大学医学部循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1/