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An approach to understand the interaction of lipoproteins and vascular endothelial cells

Research Project

Project/Area Number 04454266
Research Category

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

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKobe University

Principal Investigator

YOKOYAMA Mitsuhiro  Kobe University School of Medicine the 1st Department of Internal Medicine Professor, 医学部, 教授 (40135794)

Co-Investigator(Kenkyū-buntansha) SUEMATU Masakuni  Kobe University School of Medicine the 1st Department of Internal Medicine Assis, 医学部・附属病院, 助手 (90240853)
KAWASHIMA Yasuhiro  Kobe University School of Medicine The 1st Department of Internal Medicine Assis, 医学部, 助手 (10177678)
KAWAHARA Ysuhiro  Kobe University School of Medicine The 1st Department of Internal Medicine, 医学部・附属病院, 講師 (80169755)
ISHIKAWA Yuichi  Kobe University School of Medicine The Allied Medical Sciences Professor, 医療技術短期大学部, 教授 (90159707)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥4,300,000 (Direct Cost: ¥4,300,000)
Keywordsvascular endothelial cells / endothelium-derived relaxing factor / low density lipoprotein / high density lipoprotein / nitric synthase / protein kinase C / lysophosphatidylcholine / intracellular calcium concentration
Research Abstract

(1) Effect of lipoproteins and lysolipids on endothelium-dependent relaxation
We have demonstrated that lysophosphatidylcholine (LPC) in oxidized low density lipoprotein (ox-LDL) inhibits the synthesis of EDRF/NO in endothelial cells. LPC and ox-LDL inhibit the intracellular signal transduction which links the receptor stimulation to biosynthesis of the second massenger in endothelial cells, leading to an endothelial defect in the generation at appropriate intracellular calcium signals nesessary for activation of NO synthase. HDL reverses the ox-LDL-induced impairment of endothelium-dependent relaxation by removing LPC from ox-LDL
(2) Regulation of endothelial NO synthase (NOS)
We have purified endothelial NOS from cultured bovine aortic endothelial cells (BAECs). Endothelial NOS was mainly regulated Ca^<2+>/calmodulin in the presence of NADPH,FAD and BH_4 as cofactors. NOS activity was enhanced approximately up to three fold by PC, LPC and phosphatidylethanolamice. NOS mRNA expression was investigated in BAECs. LPC or ox-LDL enhanced NOS mRNA expression.Interferon alpha/beta increased NOS mRNA expression, but TNF-alpha inhibited it.
(3) Regulation of inducible NOS (iNOS) mRNA expression in vascular smooth muscle cells. interferon gamma, TNF alpha and interleukin-1beta each markedly increased mRNA and protein levels of iNOS in parallel with the production of nitrite. TGF-beta significantly inhibited the increase in protein levels caused by these cytokines.

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report

Research Products

(21 results)

All Other

All Publications (21 results)

  • [Publications] M.Koide: "Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells" Hypertension. 23. 45-48 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Matsuda: "High density lipoprotein reveses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation." Circ Res. 72. 1103-1109 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Ohashi: "Activation of nitric oxide synthase from cultured aortic endothelial cells by phospholipids" Biochem Biophys Res Comm. 195. 1314-1320 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Koide: "Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells" J Biol Chem. 268. 24959-24966 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Inoue: "Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells." Circ Res. 71. 1410-1421 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Hirata: "Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression." Arteriosclerosis and Thrombosis. 12. 99-105 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Koide: "Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells" Hypertension. 23. 45-48 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Matsuda: "High density lipoprotein reveses inhibitory effct of oxidized low density lipoprotein on endothelium-dependent arterial relaxation" Circ Res. 72. 1103-1109 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Ohashi: "Activation of nitric oxide synthase from cultured aortic endothelial cells by phospholipids" Biochem Biophys Res Comm. 195. 1314-1320 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] N.Inoue: "Lysophosphatidylcholine inhibits badykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells" Circ Res. 71. 1410-1421 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] K.Hirata: "Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression" Arteriosclerosis and Thrombosis. 12. 99-105 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] M.Koide: "Expression of nitric oxide synthase by cytokines in vascular smooth muscle cells" Hypertension. 23. 45-48 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Matsuda: "High density lipoprotein reveses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation." Circ Res. 72. 1103-1109 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.Ohashi: "Activation of nitric oxide synthase from cultured aortic endothelial cells by phospholipids" Biochem Biophys Res Comm. 195. 1314-1320 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Koide: "Cyclic AMP-elevating agents induce an inducible type of nitric oxide synthase in cultured vascular smooth muscle cells" J Biol Chem. 268. 24959-24966 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Y.matsuda: "High density lipoprotein reveses inhibitory effect of oxidized low density lipoprotein on endothelium-dependent arterial relaxation." Circ Res. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Koide: "Cytokine-induced expression of an inducible-type of niric oxide synthase gene in cultured vascular smooth muscle cells." FEBS Letters. (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] N.Inoue: "Lysophosphatidylcholine inhibits bradykinin-induced phosphoinositide hydrolysis and calcium transients in cultured bovine aortic endothelial cells." Circ Res. 71. 1410-1421 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] K.Hirata: "Impaired vasodilatory response to atrial natriuretic peptide during atherosclerosis progression." Arteriosclerosis and Thrombosis. 12. 99-105 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] T.Tsuda: "Angiotensin 2 Stimulates two myelin basic protein/microtubule-associated Protein 2 Kinases in culutured vascular smooth muscle cells." Circ Res. 71. 620-630 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Koide: "Endothelin-1 stimulates tyrosine phosphorylation and the activities of two mitogen-activated protein kinases in cultured vascular smooth muscle cells." J Hypertension. 10. 1173-1182 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-03-31   Modified: 2016-04-21  

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