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1998 Fiscal Year Final Research Report Summary

Analysis of Anigogenesis and Shear-Mismatching Response Based on Endothelial Cell Biomechanics

Research Project

Project/Area Number 09308034
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionThe University of Tokyo

Principal Investigator

KAMIYA Akira  Dept.of Biomedical Engineering, Graduate School of Medicine, The University of Tokyo, Professor, 大学院・医学系研究科, 教授 (50014072)

Co-Investigator(Kenkyū-buntansha) MASUDA Hirotake  Dept.of Pathology, School of Medicine, Akita Univ., Professor, 医学部, 教授 (60103462)
ANDO Joji  Dept.of Biomedical Engineering, Graduate School of Medicine, The University of T, 大学院・医学系研究科, 助教授 (20159528)
SHIBATA Masahiro  Dept.of Biomedical Engineering, Graduate School of Medicine, The University of T, 大学院・医学系研究科, 講師 (60158954)
Project Period (FY) 1997 – 1998
Keywordsshear stress / endothelial cell / angiogenesis / hemodynamics force / intravital microscope / vasodilator / 微小循環
Research Abstract

The aim of the present study was to analyze the mechanisms for physiological angiogenesis or pathological intimal thickening from a view point of vascular responses to shear stress produced by flowing blood. The effect of an increase in blood flow on new microvascular formation was studied in vivo. Using an intravital microscopic technique, we observed die process of new microvascular formation in the ear chamber of rabbits treated with alpha 1 blocker (prazosin) for 7-23 days. The prazosin-treated (blood flow-loaded) rabbits showed a marked increase in microvascular formation. The ultimate vascular density in the prazosin-treated rabbit was almost 21% higher than that in the control rabbit Various growth factors and cytokines which are secreted from endothelial cells are involved in vascular intimal thickening. The effect of shear stress on the production of cylokines by endothelial cells was investigated in vitro. Cultured human umbilical vein endothelial cells were subjected to a shear stress of 15 dynes/cm^2 for 24 h in a parallel plate type of flow-loading device and the changes in the concentration of granulocyte/macrophage-colony stimulating factor (GM-CSF) were determined by ELISA.Shear stress increased the production of GM-CSF 6-times the control level, while it had no effect on the production of other CSFs such as granulocyte-CSF and macrophage-CSF.Both run-on assay and luciferase assay demonstrated that shear stress did not affect transcription of GM-CSF gene, but actinomycin-D chase experiments revealed that the half-life of GM-CSF mRNA was significantly longer in shear-stressed cells than that in control cells. This indicates that shear stress augments GM-CSF production in endothelial cells via mRNA stabilization.

  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] S.Ichioka: "In vivo measurement of morphometric hemodynamic changes in the microcirculation during angiogenesis under chronic α1-adrenergic blocker treatment." Microvasc.Res.55. 165-174 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Ichioka: "Biological effects of magnetic fields on the microcirculatory blood flow in vivo" A preliminary report.Med.& Biol.Eng. & Comput.36. 91-95 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T.Murase: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circ.Res.83. 328-333 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Isshiki: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A.95. 5009-5014 (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] H.Watanabe: "An essential role of myosin light-chain kinase in the regulation of agonist-and fluid-flow-stimulated Ca^<2+> influx in endothelial cells." FASEB J. 12. 341-348 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K.Kosaki: "Fluid shear stress increases the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization." Circ.Res.81. 794-803 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Ando: "Flow-induced endothelial gene regulation. In “Mechanical Forces and the Endothelium"" P.I. Lelkes ed.,Harwood Academic Publishers,London(in press), (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Shibata: "A phosphorescence measurement of tissue oxygen distribution in the ratcremaster muscle." Proc.Eur.Microcirc. (P.H.Carpentier,et.al.eds.) Monduzzi Editore,Bologna, 6 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S.Ichioka, M.Shibata, K.Kosaki, Y.Sato, K.Harii, and A.Kamiya: "In vivo measurement of morphometric hemodynamic changes in the microcirculation during angiogenesis under chronic al-adrenergic blocker treatment." Microvasc.Res.55. 165-174 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Ichioka, M.Iwasaka, M.Shibata, K.Harii, A.Kamiya, and S.Ueno: "Biological effects of magnetic fields on the microcirculatory blood flow in vivo : A prelliminary report." Med.& Biol.Eng.& Comput. 36. 91-95 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Murase, N.Kume, R.Korenaga, J.Ando, T.Sawamura, T.Masaki, and T.Kita: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells." Circ.Res.83. 328-333 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Isshiki, J.Ando, R.Korenaga, H.Kogo, T.Fujimoto, T.Fujita, and A.Kamiya: "Endothelial Ca^<2+> waves preferentially originate at specific loci in caveolin-rich cell edges." Proc.Natl.Acad.Sci.U.S.A.95. 5009-5014 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Watanabe, R.Takahashi, X-X.Zhang, Y.Goto, H.Hayashi, J.Ando, M.Isshiki, M.Seto, H.Hidaka, I.Niki, and R.Ohno: "An essential role of myosin light-chain kinase in the regulation of agonist-and fluid-flow-stimulated Ca^<2+> influx in endothelial cells." FASEB J. 12. 341-348 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Kosaki, J.Ando, R.Korenaga, T.Kurokawa, and A.Kamiya: "Fluid shear stress increases the production of granulocyte-macrophage colony-stimulating factor by endothelial cells via mRNA stabilization." Circ.Res.81. 794-803 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Y.Takada, C.Kato, S.Kondo, R.Korenaga, and J.Ando: "Cloning of cDNA encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress." Biochem.Biophys.Res.Commun.240. 737-741 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] R.Korenaga, J.Ando, K.Kosaki, M.Isshiki, Y.Takada, and A.Kamiya: "Negative transcriptional regulation of the VCAM-1 gene by fluid shear stress in murine endothelial cells." Am.J.Physiol.273. C1506-C1515 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] T.Chun, H.Itoh, Y.Ogawa, N.Tamura, K.Takaya, T.Igaki, J.Yamashita, K.Doi, M.Inoue, K.Masatsugu, R.Korenaga, J.Ando, and K.Nakao: "Shear stress augments expression of C-type natriuretic peptide and adrenomedulin." Hypertension. 29. 1296-1302 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Ando, H.Tsuboi, R.Korenaga, K.Takahashi, K.Kosaki, M.Isshiki, T.Tojo, Y.Takada, and A.Kamiya: "Differential display and cloning of shear stress-responsive messenger RNAs in human endothelial cells." Biochem.Biophys.Res.Commun.225. 347-351 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Ichioka, M.Shibata, K.Kosaki, Y.Sato, K.Harii, and A.Kamiya: "Effect of shear stress on wound-healing angiogenesis in the rabbit ear chamber." J.Surg.Res.72. 29-35 (1997)

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      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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