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1994 Fiscal Year Final Research Report Summary

Bio-engineering study on the mechanism of endothelial cell responses to blood flow

Research Project

Project/Area Number 03404062
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field 医学一般
Research InstitutionInstitute of Medical Electronics, Faculty of Medicine, Univ.of Tokyo

Principal Investigator

KAMIYA Akira  Faculty-of Medicine, Univ.Tokyo, Professor, 医学部(医), 教授 (50014072)

Co-Investigator(Kenkyū-buntansha) SHIBATA Masahiro  Faculty of Medicine, Univ.Tokyo, Lecturer, 医学部(医), 講師 (60158954)
ANDO Joji  Faculty of Medicine, Univ.Tokyo, Guest Associate Professor, 医学部(医), 客員助教授 (20159528)
Project Period (FY) 1991 – 1994
KeywordsEndothelila cells / Calcium ion / Nitric oxide / Shear stress / Adhesion molecule / VCAM-1
Research Abstract

To elucidate the mechanism of vascular endothelial cell (EC) responses to blood flow, cultured ECs were exposed to controlled levels of shear stress in a flow-loading device and their responses were examined in vitro. Concretely, three different experiments were performed in this project ; 1) as regards the signal transduction of shear stress, changes in intracellular Ca^<++> concentration ([Ca^<++>]) were monitored by a calcium indicator, Fura-2, and fluorescence photomicroscopy when ECs were subjected to shear stress. 2) as to cell responses to shear stress, the production of nitric oxide, a potent vasodilator, by ECs was measured. 3) as to shear stress effect on gene expression, changes in the mRNA levels of adhesion molecules were analyzed with reverse transcriptase/polymerase chain reaction method. The results obtained are as follows.
1) Application of medium flow increased [Ca^<++>] in ECs. The response needs the presence of extracellular ATP,and at 500 nM ATP,[Ca^<++>] increased in proportion to flow rate. Flow-loading experiments using two perfusates with different viscosities revealed that flow-induced [Ca^<++>] increase in shear stress-rather that shear rate-dependent.
2) Shear stress stimulated nitric oxiide production by ECs.
3) Shear stress decreased the mRNA level of vascular adhesion molecule-1 in mouse venule ECs, and at the same time down regulated the cell surface expression.
These data suggest that vascular ECs can perceive shear stress generated by blood flow and alter their functions in both protein and gene levels, which is probably involved in flow-dependent vascular structuring and atherogenesis.

  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] J.Ando: "Shear stress inhibits the adhesion of cultured mouse endothelial cells to lymphocytes by down-regulating VCAM-1 expression" Am.J.Physiol.267. C679-C687 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Ando: "Intracellular calcium response to directly applied mechanical shearing force in cultured vascular endothelial cells" Biorheology. 31. 57-68 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] W.Yang: "Exogenous nitric oxide inhibits proliferation of cultured vascular endothelial cells" Biochem.Biophys.Res.Commun.203. 1160-1167 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] R.Korenaga: "Laminar flow stimulates ATP-and shear stress-dependent nitric oxide production in cultured bovine endothelial cells" Biochem.Biophys.Res.Commun.198. 213-219 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kamiya: "Vascular endothelial cell functions and biomechanics" Endothelium. 1. 127-130 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Ohtsuka: "The effect of flow on the expression of vascular adhesion molecule-1 by cultured mouse endothelial cells" Biochem.Biophys.Res.Commun.193. 303-310 (1993)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] A.Kamiya: "Endothelial cell responses to fluid shear stress In "Endothelium-derived factors and vascular functions"" Tomoh Masaki eds. Excerpta Medica,Tokyo, 12 (1994)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] J.Ando: "Shear stress inhibits the adhesion of cultured mouse endothelial cells to lymphocytes by down-regulating VCAM-1 expression" Am.J.Physiol.267. C679-C687 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] J.Ando: "Intracellular calcium response to directly applied mechanical shearing force in cultured vascular endothelial cells" Biorheology. 31. 57-68 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.Yang: "Exogenous nitric oxide inhibits proliferation of cultured vascular endothelial cells" Biochem.Biophys.Res.Commun.203. 1160-1167 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] R.Korenaga: "Laminar flow stimulates ATP-and shear stress-dependent nitric oxide production in cultured bovine endothelial cells" Biochem.Biophys.Res.Commun.198. 213-219 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Kamiya: "Vascular endothelial cell functions and biomechanics" Endothelium. 1. 127-130 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Ohtsuka: "The effect of flow on the expression of vascular adhesion molecule-1 by cultured mouse endothelial cells" Biochem.Biophys.Res.Commun.193. 303-310 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] A.Kamiya: Endothelial cell responses to fluid shear stress, In "Endothelium-derived factors and vascular functions". Tomoh Masaki eds. Excerpta Medica, Tokyo, 12 (1994)

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

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Published: 1999-03-09  

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