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Possible involvement of a mechanosensitive cell adhesion molecule PECAM-1 in the localization of atherosclerotic lesion.

Research Project

Project/Area Number 09670250
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

MASUDA Michitaka  National Cardiovascular Center Research Institute, Department of Structural Analysis, Section Chief, 循環器形態部, 室長 (00190364)

Co-Investigator(Kenkyū-buntansha) KUSANO Kenichi  National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 流動研究員
KANO Yumiko  National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 室長 (30214498)
OSAWA Masaki  National Cardiovascular Center Research Institute, Department of Structural Anal, 循環器形態部, 室員 (40291182)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Keywordsendothelial cell / blood vessel / atherosclerosis / PECAM-1 / tyrosine phosphorylation / SHP2 / チロシンリン酸化 / 粥状硬化
Research Abstract

1. Functions of vascular endothelial cells are regulated by mechanical environments as well as by chemical environments. The mechanical environments or mechanical signals, such as fluid shear stress and tension, may play important roles in the initiation and the progression of vascular lesions and also in their recovery processes. For example, the localization of atherosclerotic lesion is known to be related by local hemodynamic force fields. This may be explained by changes in endothelial cell characters induced by fluid shear stress.
2. We have found that an cell-cell adhesion molecule, PECAM-l, is rapidly tyrosine phosphorylated by mechanical forces such as fluid shear stress and osmotic shocks. In the first year of this project, we found that the phosphorylated PECAM-l served a major plasma membrane anchoring site for a cytoplasmic protein tyrosine phosphatase, SH-PTP2 (SHP2, Syp). SH-PTP2 acts as a positive mediator in a MAP kinase (Erk) cascade. We are gathering evidence showing that the PECAM-l mediated mechanosignal transduction is involved in the Erk activation.
3. The Erk activation plays a major role in "slow" endothelial responses to flow including changes in gene expression. Our results provide biochemical bases for future analyses of "very slow" flow-modulated responses such as the initiation and the progression of atherosclerotic lesions.
4. We failed to detect the mechanosensitive PECAM-l tyrosine phosphorylation in various cell lines transfected with bovine PECAM-l except for human endothelial cells. This result suggests the presence of specific kinase(s) for PECAM-l in endothelial cells. Our current project is to identify the putative PECAM-l kinase(s).

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] 大沢正輝: "Tyrosine phosphorylation of platelet endothelial cell adhescor molecule-1(PECAM-1, CD31)in mechanically stimolated vascularendotheial cells" Eur.J.Cell Biol. 72. 229-237 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 増田道隆: "Platelet endotheliol cell adnesion molecule-1 is a major SH-PTP2 binding protein in vasculav endothelial cells." FEBS Letters. 408. 331-336 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ochi, H.: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphati dylcholine in cultured erdothelial cells." Biochem.Biophys.Res.Comm.243. 862-868 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 増田道隆: "流れ刺激受容のメカニズムとPECAM-1" 医学のあゆみ. 182. 303-308 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 藤原敬己: "Shear stress-内皮細胞による流れ感知とPECAM-1" 実験医学. 16. 712-717 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大沢正輝: "内皮細胞におけるPECAM-1のリン酸化/脱リン酸化" 血管と内皮. 8. 124-132 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 増田道隆: "Cell volvme regulation : The molecular mechanism and volume sensing machinery" Elsevier Science B.V., Amsterdam, 214 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 藤原敬己: "Tissue engineering for therapeutic use 2." Elsevier Science B.V., Amsterdam, 146 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osawa, M.et al.: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) in mechanically stimulated vascular endothelial cells." Eur.J.Cell Biol.72. 229-237 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuda, M.et al.: "Platelet endothelial cell adhesion molecule-1 is a major SH-PTP2 bindig protein in vascular endothelial cell." FEBS Letters. 408. 331-336 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ochi, H.et al.: "Tyrosine phosphorylation of platelet endothelial cell adhesion molecule-1 induced by lysophosphatyidylcholine in cultured endothelial cells." Biochem.Biophys.Res.comm.243. 862-868 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuda, M.et al.: "The Mechanism of flow sensing and PECAM-1 (in Japanese.)" Journal of Clinical and Experimental Medicine (IGAKU NO AYUMI). 182. 303-308 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujiwara, K.et al.: "Shear stress-Involvement of PECAM-1 in the flow-sensing of endothelial cells. (in Japanese)" Experimental Medicine(JIKKEN IGAKU). 16. 712-717 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Osawa, M.et al.: "Tyrosine phosphorylation and dephosphorylation of PECAM-1 in vascular endothelial cells.(in Japanse.)" Blood Vessel and Endothelium (KEKKAN TO NAIHI). 8. 124-132 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Masuda, M.et al.: "Platelet endothelial cell adhesion molecule-1 (PECAM-1, CD31) is involved in mechano-signal transduction in endothelial cells." In Cell Volume Regulation : The Molecular Mechanism and Volume Sensing Machinery. (Excerpta Medica・International Congress Series 1164), Y.Okada, ed., pp23-33, Elsevier Science B.V., Amsterdam.(1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fujiwara, K.et al.: "Flow sensing by vascular endothelial cells : a model for cellular mechanosensing." In Tissue Engineering for Therapeutic Use 2, Ikada, Y.and Enomoto, S.eds., pp31-41, Elsevier Science B.V., Amsterdam. (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大澤 正輝: "Tyrosine phosphorylation of platelet andothelial adhesion molecule-1 (PECAM-1,CD31) in mechanically stimulated vascular-endothelial cells." Eur.J.Cell Biol.72. 229-237 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 増田 道隆: "Platelet endothelial cell adhesion molecule-1 is a major SH-PTD2 binding protein in vasculr endothelial cells." FEBS Letters. 408. 331-336 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ochi,H.: "Tyrosine phosphorybtion of platelet endothelial cell adhesion molecule-1 induced by lysophosphatydyl choline in cuttured endothelial cells" Biochem.Biophys.Res.Comm.243. 862-868 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 増田 道隆: "流れ刺激受容のメカニズムとPECAM-1" 医学のあゆみ. 182. 303-308 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤原 敬己: "Shear-stress-内皮細胞による流れ感知とPECAM-1" 実験医学. 16. 712-717 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大澤 正輝: "内皮細胞におけるPECAM-1のリン酸化/脱リン酸化" 血管と内皮. 8. 124-132 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 増田 道隆: "Cell volexme regulation:The molecular mechanism and volume sensing machinary" Elsevier Science B.V.,Amsterdam, 214 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 藤原 敬己: "Tissue engineering for theraputic use 2" Elsevier Science B.V.,Amsterdam, 146 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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