Promoting vascular differentiation could be a new therapeutic strategy for patent ductus arteriosus in premature infant s

• Project/Area Number: 19591285
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Embryonic/Neonatal medicine
• Research Institution: Yokohama City University
• Principal Investigator: IWASAKI Shiho Yokohama City University, 医学部, 准教授 (10347338)
• Co-Investigator(Kenkyū-buntansha): MINAMISAWA Susumu 横浜市立大学, 医学研究科, 客員教授 (40257332)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 動脈管 / 内膜肥厚 / ヒアルロン酸

Research Abstract

現在、動脈管治療はプロスタグランジン(PG)標的であるが副作用が大きい。胎児期にはPGが動脈管を拡張しつつ、ヒアルロン酸(HA)産生を促進し内膜肥厚を誘導している。PGはアデニールシクラーゼ(AC)を活性化し作用するため、ACを標的としたより選択的な薬剤開発を目的とした。動脈管において高発現していたAC2、5、6の刺激薬での検討で、AC5/6刺激薬にはPGと同様に血管拡張作用とHA産生作用があるが, AC2刺激薬は血管拡張作用が主である事が示唆された

Research Products

• [Journal Article] Prostaglandin E2-activated Epac Promotes Neointimal Formation of the Rat Ductus Arteriosus by a Process Distinct from That of cAMP-dependent Protein Kinase A. (2008)
  • Author(s): Yokoyama U, Minamisawa S, Quan H, Akaike T, Suzuki S, Jin M, Jiao Q, Watanabe M, Otsu K, Iwasaki S, Nishimaki S, Sato M, Ishikawa Y
  • Journal Title: J Biol Chem 1283(42) Pages: 28702-9
  • Peer Reviewed
• [Journal Article] Y.Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight (2008)
  • Author(s): Okumura S, Tsunematsu T, Bai Y, Jiao Q, Ono S, Suzuki S, Kurotani R, Sato M, Minamisawa S, Umemura S, Ishikawa
  • Journal Title: J Appl Physiol 105(1) Pages: 173-9
  • Peer Reviewed
• [Journal Article] Blood flow velocities in the anterior cerebral artery and basilar artery in asphyxiated infants (2008)
  • Author(s): Nishimaki S, Iwasaki S, Minamisawa S, Seki K, Yokota S
  • Journal Title: J Ultrasound Med 27(6) Pages: 955-60
  • Peer Reviewed
• [Journal Article] Sarcalumenin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum (2008)
  • Author(s): Shimura M, Minamisawa S, Takeshima H, Jiao Q, Bai Y, Umemura S, Ishikawa Y
  • Journal Title: Cardiovasc Res 77(2) Pages: 362-70
  • Peer Reviewed
• [Journal Article] Transient neonatal diabetes mellitus in extremely preterm infant (2008)
  • Author(s): Nishimaki S, Yukawa T, Makita Y, Honda H, Kikuchi N, Minamisawa S, Yokota S
  • Journal Title: Arch Dis Child Fetal Neonatal Ed 93(3)
  • Peer Reviewed
• [Journal Article] ac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration (2008)
  • Author(s): Yokoyama U, Minamisawa S, Quan H, Akaike T, Jin M, Otsu K, Ulucan C, Wang X, Baljinnyam E, Takaoka M, Sata M, Ishikawa Y
  • Journal Title: Am J Physiol Heart Circ Physiol 295(4)
  • Peer Reviewed
• [Journal Article] Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells (2008)
  • Author(s): AMisra S, Obeid LM, Hannun YA, Minamisawa S, Berger FG, Markwald RR, Toole BP, Ghatak S
  • Journal Title: J Biol Chem 283(21) Pages: 14335-44
  • Peer Reviewed
• [Journal Article] 心筋症の分子生物学 (2008)
  • Author(s): 赤池徹、南沢享
  • Journal Title: 小児科 49(6) Pages: 795-801
• [Journal Article] Prostaglandin E2-activated Epac Promotes Neointimal Formation of the Rat Ductus Arteriosus by a Process Distinct from That of cAMP-dependent Protein Kinase A (2008)
  • Author(s): 岩崎 志穂
  • Journal Title: The Journal of Biological Chemistry 283 Pages: 28702-28709
  • Peer Reviewed
• [Journal Article] Blood flow velocities in the anterior cerebral artery and basilar artery in asphyxiated infants. (2008)
  • Author(s): 岩崎 志穂
  • Journal Title: J Ultrasound Med. 27 Pages: 955-960
  • Peer Reviewed
• [Journal Article] Sarcalumenin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum. (2008)
  • Author(s): 南沢 享
  • Journal Title: Cardiovasc Res 77 Pages: 362-370
  • Peer Reviewed
• [Journal Article] Transient neonatal diabetes mellitus in extremely preterm infant. (2008)
  • Author(s): 南沢 享
  • Journal Title: Arch Dis Child Fetal Neonatal Ed. 93 Pages: 240-241
  • Peer Reviewed
• [Journal Article] Hyaluronan constitutively regulates activation of COX-2-mediated cell survival activity in intestinal epithelial and colon carcinoma cells. (2008)
  • Author(s): 南沢 享
  • Journal Title: J Biol Chem. 283 Pages: 14335-14344
  • Peer Reviewed
• [Journal Article] Epacl is upregulated during neointima formation and promotes vascular smooth muscle cell migration. (2008)
  • Author(s): 南沢 享
  • Journal Title: Am J Physiol Heart Circ Physiol. 295 Pages: 547-555
  • Peer Reviewed
• [Journal Article] Interleukin-15 inhibits smooth muscle cell proliferation and hyaluronan production in rat ductus arteriosus (2007)
  • Author(s): Iwasaki S, Minamisawa S, Yokoyama U, Akaike T, Hong Q, Nagasihima Y, Nishimaki S, Ishikawa Y, Yokota S.
  • Journal Title: Ped Res 62(4) Pages: 392-8
  • Peer Reviewed
• [Journal Article] Maternal vitamin A alters gene profiles andstructural maturation of the rat ductus arteriosus (2007)
  • Author(s): Yokoyama U, Sato Y, Akaike T, Ishida S, Sawada J, Nagao, T, Quan H, Jin M, Iwamoto M, Yokota S, Ishikawa Y, Minamisawa S.
  • Journal Title: Physiol Genomics 31(1) Pages: 139-57
  • Peer Reviewed
• [Journal Article] Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy (2007)
  • Author(s): Ulucan C, Wang X, Baljinnyam E, Bai YZ, Okumura S, Sato M, Minamisawa S, Hirotani S, Ishikawa Y.
  • Journal Title: J Physiol Heart Circ Physiol 293(3)
  • Peer Reviewed
• [Journal Article] Dopamine induces apoptosis in young, but not in neonatal, neurons via Ca 2+-dependent signal (2007)
  • Author(s): Iwatsubo K, Suzuki S, Li C, Tsunematsu T, Nakamura F, Okumura S, Sato M,! Minamisawa S, Toya Y, Umemura S, Ishikawa Y.
  • Journal Title: Am J Physiol Cell Physiol 293(5)
  • Peer Reviewed
• [Journal Article] 成長ホルモン及びその関連因子は動脈管の血管成熟・分化を促すか? (原著論文) (2007)
  • Author(s): 南沢享, 赤池徹, 金美花, 全紅, 焦其彬,岩崎志穂
  • Journal Title: 成長科学協会研究年報(0386-7617) 30 Pages: 229-235
• [Presentation] Animal model of ductus arteriosus : A new role of prostaglandin E.2008Pediatric Research Workshop " What Animal Model Can Do in Pediatric Research " (2008)
  • Author(s): Minamisawa S
  • Organizer: by Taiwan Pediatric Association
  • Place of Presentation: Taipei
  • Year and Date: 2008-09-13
• [Presentation] Animal model of ductus arteriosus: A new role of prostaglandin E. (2008)
  • Author(s): 南沢 享
  • Organizer: 2008 Pediatric Research Workshop 「What Animal Model Can Do in Pediatric Research」 by Taiwan Pediatric Association.
  • Place of Presentation: Taipei
  • Year and Date: 2008-09-13
• [Presentation] プロスタグランジンによる血管内膜肥厚 : A new role for an old friend. 岩手医科大学先端医療研究センター公開シンポジウム (2008)
  • Author(s): 南沢享
  • Organizer: 「バイオイメージングと分子生物学による脳・血管解明-健康増進に向けた最先端研究
  • Place of Presentation: 盛岡
  • Year and Date: 2008-07-19
• [Presentation] プロスタグランジンによる血管内膜肥厚:A new role for an old friend. (2008)
  • Author(s): 南沢 享
  • Organizer: 岩手医科大学先端医療研究センター公開シンポジウム「バイオイメージングと分子生物学による脳・血管解明-健康増進に向けた最先端研究」
  • Place of Presentation: 盛岡
  • Year and Date: 2008-07-19
• [Presentation] 構造変化から見た動脈管閉鎖機構 (2008)
  • Author(s): 南沢享
  • Organizer: 第7回心臓血管発生研究会第7回心臓血管発生研究会
  • Place of Presentation: 郡山
  • Year and Date: 2008-07-05
• [Presentation] Prostaglandin E-cAMP signals promote neointimal cushion formation in the ductus arteriosus (2008)
  • Author(s): 南沢享
  • Organizer: 第85回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Presentation] Regulation of activity of sarcoplasmic reticulum calcium ATPase in the failing heart (2008)
  • Author(s): 南沢享
  • Organizer: The 72th Annual Scientific meeting of the Japanese Circulation Society
  • Place of Presentation: 東京
  • Year and Date: 2008-03-27
• [Presentation] Prostaglandin E2 in the Ductus Arteriosus : A New Role for an Old Friend. CNSI-ASMeW Joint Symposium on Nano-scale Research into Biosenors (2008)
  • Author(s): Minamisawa S
  • Organizer: Biomaterials, and Nanotoxicology
  • Place of Presentation: Los Angels, USA
  • Year and Date: 2008-03-06
• [Presentation] ラット胎児動脈管に対するインターロイキン15の作用 (2007)
  • Author(s): 岩崎志穂, 西巻滋, 横田俊平
  • Organizer: 第52回日本未熟児新生児学会
  • Place of Presentation: 高松
• [Presentation] cAMP-dependent neointimal cushion formation in rat ductus arteriosus. The Capri Science Conferences "Translational Approaches to Cardiovascular Research" Meeting (2007)
  • Author(s): Minamisawa S, Yokoyama U, Akaike T, Hong Q, Segi-Nishida E, Iwasaki S, Ghatak S, Misra S, Toole BP, Sugimoto Y, Ishikawa Y.
  • Organizer: selected oral presentation
  • Place of Presentation: Capri, Italy
• [Presentation] cAMP-dependent Intimal Cushion Formation Of the Rat Ductus Arteriosus : The Role Of Epac (2007)
  • Author(s): Quan H, Yokoyama U, Watanabe M, Akaike T, Otsu K, Iwasaki S, Ishikawa Y, Minamisawa S.
  • Organizer: The 80^<th> annual scientific meeting of the Ameican Heart Association
  • Place of Presentation: Orlando, Orange County Convention Center
• [Book] 動脈管の閉鎖機転 : 細胞外基質の役割, (山口徹、高本眞一、中澤誠、小室一成編集*) Annual Review循環器2007 (2007)
  • Author(s): 南沢享
  • Publisher: 中外医学社
• [Book] 動脈管閉鎖の分子機構, (山岸敬幸、白石公編集*) 先天性心疾患を理解するための臨床心臓発生学 (2007)
  • Author(s): 横山詩子、南沢享
  • Publisher: メジカルビュー社