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2003 Fiscal Year Final Research Report Summary

Molecular Pathophysiological Study on Endothelial Function Occurring during Vascular Remodeling

Research Project

Project/Area Number 13307009
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SUEISHI Katsuo  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (70108710)

Co-Investigator(Kenkyū-buntansha) YONEMITSU Yoshikazu  KYUSHU UNIVERSITY, University Hospital, Lecturer, 講師 (40315065)
NAKAGAWA Kazunori  KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Lecturer, 大学院・医学研究院, 講師 (50217668)
Project Period (FY) 2001 – 2003
Keywordsvascular remodeling / atherosclerosis / angiogenesis / angiogenic hierarchy / FGF-2 / SeV / Gene transfer / tissue stem cell
Research Abstract

1.Endothelial function in physiological and pathological vascular remodeling
From studies concerning atherosclerosis, mechanism of functional angiogenesis, differentiation mechanism of hepatic stem cell, the main results obtained were as follows :
1)Atherosclerosis and angiogenesis : intimal neovascularization related to VEGF-A and -C expression was equivalent to a histopathological hallmark of active atherogenesis, and we propose "inflammation-repair hypothesis" for atherogenesis.
2)Molecular mechanism of functional angiogenesis : FGF-2 hierarchically enhanced the expression of VEGF,HGF,PDGF and others in a hypoxic tissues, leading to the integrated angiogenesis associated with structural and functional interaction between endothelial-pericytes(smooth muscle cells).
3)Differentiation mechanism of hepatic stem cells : FLK-1-positive cells in mouse fetuses possessed the pluripotent differentiation activities into hepatocytes and bile ducts, and blood vessels under HGF+EGF and VEGF+PDGF-BB stimulation, respectively.
2.Biological properties of novel gene transfer vectors and their clinical application
Using recombinant SeV and SIV vectors with several reporter and target genes(FGF-1,-2,-10,VEGF-A,PEDF,sprouty-2,soluble PDGF receptor etc), biological and pathbphysiological characteritics of spatial and time-sequential transfer/expression efficacy of these vectors were analyzed and we are exploiting the novel strategies on gene therapy.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Ikeda Y, et al.: "Simian immunodeficiency virus-based lentivirus vactor for retinal gene transfer : a preclinical safety study in adult rats."Gene Therapy. 10(14). 1161-1169 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ameri A, et al.: "Myocardial fibrosis in mice with over-expression of human blood coagulation factor IX : Myocardial infarction model."Blood. 101. 1871-1873 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Morishige K: "Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo."Cardiovasc Res. 57(2). 572-585 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Onimaru M, et al.: "Fibroblast growth factor-2 gene transfer can stimulate hepatocyte growth factor expression irrespective of hypoxia-mediated downregulation in ischemic limbs."Circ Res. 91. 723-730 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nakashima Y, et al.: "Distributions of diffuse intimal thickening in human arteries : Preferential expression in atherosclerosis-prone arteries from an early age."Virchow Arch. 441. 279-288 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Masaki I, et al.: "Angiogenic gene therapy for experimental critical limb ischemia. Acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2."Circ Res. 90. 966-973 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda Y, Goto Y, Yonemitsu Y, Miyazaki M, Sakamoto T, Ishibashi T, Tabata T, Ueda Y, Hasegawa M, Tobimatsu S, Sueishi K.: "Simian immunodeficiency virus-based lentivirus vactor for retinal gene transfer : a preclinical safety study in adult rats."Gene Therapy. 10. 1161-1169 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ameri A, Kurachi S, Sueishi K, Kurachi K.: "Myocardial fibrosis in mice with over-expression of human blood coagulation factor IX : Myocardial infarction model."Blood. 101. 1871-1973 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Morishige K, Shimokawa H, Matsumoto Y, Eto Y, Uwatoku T, Abe K, Sueishi K, Takeshita A: "Overexpression of matrix metalloproteinase-9 promotes intravascular thrombus formation in porcine coronary arteries in vivo."Cardiovasc Res. 57. 572-585 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Onimaru M, Yonemitsu Y, Tanii M, Nakagawa K, Masaki I, Okano S, Ishibashi H, Shirasuna K, Hasegawa M, Sueishi K.: "Fibroblast growth factor-2 gene transfer can stimulate hepatoeyte growth factor expression irrespective of hypoxia-mediated downregulation in ischemic limbs."Circ Res. 91. 923-930 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakashima Y, Chen Y-X, Kinukawa N, Sueishi K.: "Distributions of diffuse intimal thickening in human arteries : Preferential expression in atherosclerosis-prone arteries from an early age."Virchow Arch. 441. 279-288 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Masaki I, Yonemitsu Y, Yamashita A, Sata S, Tanii M, Komori K, Nakagawa K, Hou X, Nagai Y, Hasegawa M, Sugimachi K, Sueishi K.: "Angiogenic gene therapy for experimental critical limb ischemia. Acceleration of limb loss by overexpression of vascular endothelial growth factor 165 but not of fibroblast growth factor-2."Circ Res. 90. 966-973 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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