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Developmental defects of coronary vasculature in rat embryos administered bis-diamine and WKY/NCrj rat embryos

Research Project

Project/Area Number 11670756
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionShiga University of Medical Science

Principal Investigator

NAKAGAWA Masao  Shiga University of Medical Science, Assistant Professor, 医学部, 講師 (40188909)

Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordswhole embryo culture / coronary artery / Bis-diamine / neural crest cell / tenascine / V-CAM / WKY / NCrj rat / Confocal laser scanning microscopy / NCrj ラット / 冠動脈原基 / 動脈幹分割 / 冠血管 / 心外膜
Research Abstract

1. A single 200-mg dose of bis-diamine was administered to pregnant Wister rats at 10.5 days of gestation. Fifty-two embryos from 10 mother rats underwent morphological analysis of the coronary arteries. Conotruncal anomalies were detected in 48 of 52 embryos, and an aplastic or hypoplastic left coronary artery was found in all of them.
2. Coronary vasculature was first detected in the heart of at 14.5 embryonic day (ED) control rat embryo. However, in the herats of bis-diamine treated embryos, poor promotion of epicardial-endothelial transformation was revealed at ED 14.5, 15.5,16.5, and 17.5, causing abnormal development of the coronary vasculature. V-CAM and tenascine were less expressed in the coronary vascular endothelial cells. Sinusoids were widely and deeply extended in the thin ventricular wall.
3. Developmental analysis of the early bis-diamine treated rat embryos using whole embryo culture, disclosed a markedly elongated outflow tract and enlarged ventricle with thin myocardial wall before the truncal division. Histological examinations detected no coronary buds and sparse N-CAM positive cells around the arterial trunk. This was also the case with the early WKY/NCrj rat embryos.
4. When bis-diamine was administered to the 10, 11, and 12 pregnant day mother rats, abnormal conotruncal division was seen in 0%, 93%, and 32% of the embryos, respectively. Furthermore, anomalous coronary arteries were detected only when bis-diamine was administered on 11 and 12 pregnant day, and the incidence was coincident with that of anomalous truncal division.
Although not being able to clarify whether neural crest cells play a role in coronary bud formation, these studies suggested that abnormal truncal division and pericardial development caused anomalous coronary vascular formation and distribution.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Hidetoshi Fujino,: "Immunohistochemical distribution of HNK-1 and N-CAM in rat embryos treated with bis-diamine."Cong Anom. 39. 281-293 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masao Nakagawa: "Tetracuspid aortic valve associated with a 22q11.2 microdeletion"Am J Med Genet. 93(1). 74-75 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masahiko Okuno: "Expressional patterns of cytokines in a murine model of acute myocarditis : early expression of cardiotrophin-1."Lab Invest. 80. 433-440 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Setsuko Nishijima: "Teratogenic effect of bis-diamine on early embryonic rat heart : an in vitro study"Teratology. 62(2). 115-122 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kumiyo Yagi-Ono: "Absent right superior caval vein associated with partial trisomy 18."Hereditas. 132. 255-256 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masao Nakagawa: "Teratogenic effect of bis-diamine on embryonic rat heart"Cong Anom. 40. 157-161 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masao Nakagawa: "Etiology and Morphogenesis of Congenital Heart Disease, Clark EB, Markwald RR, Takao A, Nakazawa M eds,."Futura Publishing Co (分担執筆). 389 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sato A: "Thrombocytopenia after human herpesvirus-7 infection in a patient with DiGeorge syndrome."J Pediatr Hematol Oncol. 21. 171-172 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Ebstein's anomaly associated with trisomy 9p."Clin Genet. 55. 383-385 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Detection and evaluation of asymptomatic myocarditis in schoolchildren ; report of four cases."Chest. 116. 340-345 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Doppler echo-cardiographic evaluation of the hemodynamics in absent aortic valve."Can J Cardiol. 15. 1283-1286 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujino H: "Immunohistochemical distributionof HNK-1 and N-CAM in rat embryos treated with bis-diamine."Cong Anom. 39. 281-293 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Severe hemolytic anemia following high-dose intravenous immunoglobulin administration in a patient with Kawasaki disease."Am J Hematol.. 160. 161 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Tetracuspid aortic valve associated with a 22q11.2 microdeletion"Am J Med Genet. 93. 74-75 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Okuno M: "Expressional patterns of cytokines in a murine model of acute myocarditis : early expression of cardiotrophin-1."Lab Invest. 80. 433-440 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nishijima S: "Teratogenic effect of bis-diamine on early embryonic rat heart : an in vitro study."Teratology. 62. 115-122 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yagi-Ono K: "Absent right superior caval vein associated with partial trisomy 18."Hereditas. 132. 255-256 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Effects of intracoronary tissue-type plasminogen activator treatment in Kawasaki disease and acute myocardial infarction"Cardiology. 94. 52-57 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Teratogenic effect of bis-diamine on embryonic rat heart"Cong Anom. 40. 157-161 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Bernard-Soulier syndrome associated with 22q11.2 microdeletion."Am J Med Genet. (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa M: "Effects of Bis-diamine on Cardiovascular Development in an Early Rat Embryo : in vivo and in vitro Morphological Analysis, Futura Publishing Co"Etiology and Morphogenesis of Congenital Heart Disease, Clark EB, Markwald RR, Takao A, Nakazawa M eds.. 181-184 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Masao Nakagawa: "Teratogenic effect of bis-diamine on embryonic rat heart"Cong Anom. 40. 157-161 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masao Nakagawa: "Tetracuspid aortic valve associated with a 22q11.2 microdeletion"Am J Med Genet. 93・(1). 74-75 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Setsuko Nishijima: "Teratogenic effect of bis-diamine on early embryonic rat heart : an in vitro study."Teratology. 62・(2). 115-122 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masahiko Okuno: "Expressional patterns of cytokines in a murine model of acute myocarditis : early expression of cardiotrophin-1."Lab Invest. 80. 433-440 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kumiyo Yagi-Ono: "Absent right superior caval vein associated with partial trisomy 18"Hereditas. 132. 255-256 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 中川雅生: "今求められる心臓発生、心奇形発生に関する研究のさらなる展開"日小循誌. 15・(5・6). 646-647 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masao Nakagawa: "Etiology and Morphogenesis of Congenital Heart Disease, Clark EB, Markwald RR, Takao A, Nakazawa M eds."Futura Publishing Co (分担執筆). 389 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hidetoshi Fujino: "Immunohistochemical distribution of HNK-1 and N-CAM in rat embryos treated with bis-diamine"Congenital Anomalies.. 39・4(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Setsuko Nishijima: "Teratogenic effect of bis-diamine on early embryonic rat heart: an in vitro study"Teratology.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masahiko Okuno: "Expressional patterns of cytokines in a murine model of acute myocarditis: early expression of cardiotrophin-1"Lab Invest.. 80・3(in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masao Nakagawa: "Tetracuspid aortic valve associated with a 22q11.2 microdeletion"Am J Med Genet.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masao Nakagawa: "Ebstein's anomaly associated with trisomy 9p"Clin Genet. 55・5. 383-385 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masao Nakagawa: "Doppler echocardiographic evaluation of the hemodynamics in absent aortic valve"Can J Cardiol. 15・11. 1283-1286 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Masao Nakagawa: "Etiology and Morphogenesis of Congenital Heart Disease. Clark EB, Markwald RR, Takao A, Nakazawa M eds"Futura Publishing Co. (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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