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Effects of oxidized low density lipoprotein on vascular endothelial and smooth muscle cells

Research Project

Project/Area Number 03670460
Research Category

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

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

Principal Investigator

KUGIYAMA Kiyotaka  Kumamoto University Hospital, Division of Cardiology, Assistant Professor, 医学部附属病院, 助手 (00225129)

Co-Investigator(Kenkyū-buntansha) OGAWA Hisao  Kumamoto University Hospital, Division of Cardiology, Lecturer, 医学部附属病院, 講師 (50177135)
YASUE Hirofumi  Kumamoto University Hospital, Division of Cardiology, Professor, 医学部附属病院, 教授 (40174502)
Project Period (FY) 1991 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsOxidized LDL / endothelial cells / endothelium-dependent vasorelaxation / lysophosphatidylcholine / fibrinolysis / intercellular adhesion molecule-1 / protein kinase C / Intercellular adhesion molecule-1 / Polymorphonuclear Leukecyte / endothelial cell / oxidized LDL / endothelin / fibrinolysis / protein kinase C
Research Abstract

Lysophosphatidylcholine (LPC) transferred from oxidatively modified low density lipoprotein (Ox-LDL) to the endothelial surface membrane has been shown to produce a selective unresponsiveness to cell surface receptor-regulated endothelium-dependent relaxation (EDR) in the rabbit aorta and porcine coronary artery. To determine its mechanism, the effects of LPC or Ox-LDL on intracellular signals in endothelial cells were examined. The results from this experiment indicate that LPC inhibits the early transmembrane signaling pathway in endothelial cells, and Protein Kinase C (PKC) activation could at least partially be involved in the negative regulation by LPC. These intracellular actions of LPC may play a role in the mechanism of the LPC-induced impairment of EDR in response to cell surface receptor-mediated stimulations.
To determine whether Ox-LDL modulates endothelial fibrinolytic system, levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) a … More ntigens in the conditioned medium were measured by ELISA. The results indicate that Ox-LDL stimulates PAI-1 release by the transferable hydrophilic lipid(s) in Ox-LDL, especially LPC, while Ox-LDL inhibits t-PA release by 25-hydroxycholesterol and 7-ketocholesterol or other transferable lipid(s) from Ox-LDL to albumin rather than LPC. Thus, lipid products in Ox-LDL may impair endothelial fibrinolysis. We further examined the effects of Ox-LDL on the secretion of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells (porcine aortic endothelial cells and human umbilical vein endothelial cells), considering the possible relevance of ET-1 to the atherosclerosis and hypercholesterolemia. The results show that LPC in Ox-LDL causes suppression of ET-1-LI release, which may counteract the vasoconstricitve properties of atherosclerotic arteries. Furthermore, LPC in Ox-LDL causes the increase of the endothelial adhesiveness to polymorphonuclear leukocytes (PMNs), which augments PMNs-induced impairment of EDR in porcine coronary artery. This is due to increased expression of intercellular adhesion molecule-1 in endothelium of the porcine coronary artery, and the activation of PKC by LPC in Ox-LDL may at least in part be involved in these mechanisms. Less

Report

(3 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Earl L.Mangin Jr,et al.: "Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta" Circulation Research. 72. 161-166 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama,et al.: "Lysophosphatidylcholine inhibits surface receptor-mediated intra-cellular signals in endothelial cells by a pathway involving protein kinase C activation" Circulation Research. 71. 1422-1428 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Michihisa Jougasaki et al.: "Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells" Circulation Research. 71. 614-619 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama,et al.: "Stimulation of plasminogen activator inhibitor-1(PAI-1)and inhibition of tissue plasminogen activator(tPA)release from endothelial cells by lipid products in oxidized LDL(Ox-LDL)" Circulation. 86suppl.211- (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Seigo Sugiyama,et al.: "Lysolecithin(LPC)in Oxidized LDL.(Ox-LDL)incresed susceptibility to polymorphonuclear leukocytes(PMN)-induced endothelial dys-function" Circulation. 86suppl.490- (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Earl L Mangin Jr, et al.: "Effects of oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta" Circulation Research. 72. 161-166 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama, et al.: "Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation" Circulation Research. 71. 1422-1428 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Michihisa Jougasaki, et al.: "Suppression of endothelin-l secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells" Circulation Research. 71. 614-619 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kiyotaka Kugiyama, et al.: "Stimulation of PAI-1 and inhibition of tPA release from endothelial cells by a lipid products in oxidized LDL" Circulation. (suppl. I) 86. 490 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Seigo Sugiyama, et al.: "Lysolecithin in Ox-LDL increased susceptibility to polymorphonuclear leukocytes (PMN)-induced endothelial dysfunction" Circulation. 86 (suppl-I). 490 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Earl L.Mangin Jr,et al.: "Effects of lysolipids and oxidatively modified low density lipoprotein on endothelium-dependent relaxation of rabbit aorta" Circulation Research. 72. 161-166 (1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kiyotaka Kugiyama,et al.: "Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation" Circulation Research. 71. 1422-1428 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Michihisa Jougasaki et al.: "Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells" Circulation Research. 71. 614-619 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Kiyotaka Kugiyam,et al.: "Stimulation of plasminogen activator inhibitor-1 (PAI-1) and inhibition of tissue plasminogen activator (tPA) release from endothelial cells by lipid products in oxidized LDL (Ox-LDL)" Circulation. 86 suppl.I. 211 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Seigo Sugiyama,et al.: "Lysolecithin (LPC) in Oxidized LDL (Ox-LDL) incresed susceptibility to polymorphonuclear leukocytes (PMN)-induced endothelial dys-function" Circulation. 86,suppl.I. 490- (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Masamichi Ohgushi: "Staurosporine,a potent inhibitor of protein kinase C,prevents impairment of endotheliumdependent relaxation by oxidized LDL in pig coronary arteries" Circulation. 84. II-115 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kyotaka Kugiyama: "Lysophosphatidylcholine inhibits surface receptormediated intracellular signals in human endothelia cells by a pathway involving protein kinase C activation" Circulation. 84. II-431 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Michihisa Jougasaki: "Suppression of endothelin secretion by lysophosphatidylcholine in oxidized LDL" Circulation. 84. II-435 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kiyotaka Kugiyama: "Atrial and brain natriuretic peptides(ANP and BNP)prevent endothelial cytotoxicity of lysophosphatidylcholine" Circulation. 84. II-629 (1991)

    • Related Report
      1991 Annual Research Report

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Published: 1991-04-01   Modified: 2016-04-21  

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