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Platelet and atherosclerosis, with special reference to interaction between platelets and lipoproteins.

Research Project

Project/Area Number 02454515
Research Category

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

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionYamanashi Medical College

Principal Investigator

KUME Shoji  Yamanashi Medical College, Department of Laboratory Medicine, Professor., 医学部, 教授 (50010492)

Co-Investigator(Kenkyū-buntansha) OZAKI Yukio  Yamanashi Medical College, Department of Laboratory Medicine, Associate Professo, 医学部, 助教授 (30134539)
TERAMOTO Tamio  Tokyo University School of Medicine, 1 st Department of Internal Medicine, Assis, 医学部, 助手 (20133077)
Project Period (FY) 1990 – 1992
Project Status Completed (Fiscal Year 1992)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1992: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1991: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsLDL / HDL / platelet / hyperlipidemia / apoE / cholesterol / liposome / リポソーム / リポソ-ム / 膜 / 動脈硬化 / highーdensity lipoprotein / lowーdensity lipoprotein / アポ蛋白E / 血小板凝集
Research Abstract

1) Effect of low-density lipoprotein (LDL) on platelet function. LDL(d=1.019-1.050) binds to human platelets with the dissociation constant (Kd) of 58nM and 1750 binding sites per platelet. LDL at a concentration under 1mg/ml induces a transient increase in intracellular Ca^<2+> concentration and a shape change of human platelets, but does not release granules, induce thromboxane B_2 formation or protein phosphorylation. LDL at a concentration of 100mug/ml which is near Kd of LDL-binding had a maximal stimulatory effect on agonist-induced platelet aggregation. LDL binding on platelets is Ca^<2+>-independent and displaced by high density lipoprotein (HDL). These results suggest that LDL enhances agonist-induced platelet activation via platelet-type LDL receptors differing from classical LDL receptors.
2) Effect of high-density lipoprotein (HDL) on platelet function Apolipoprotein E -(ApoE-) rich HDL of normal subjects and hyperalphalipoproteinemic patients, showed marked inhibitory effects on platelet aggregation and ATP release as compared with apoE-poor HDL, suggesting that apoE has inhibitory effects on platelet function. Dimyristoyl phosphatidylcholine liposome with apoE (apoE・DMPC) also inhibited platelet aggregation, and incubation of washed platelets with apoE・DMPC resulted in the release of cholesterol into the supernatant. These results suggest that apoE plays a major role in the inhibitory effect of apoE-rich HDL on platelet function, presumably due to the release of cholesterol from the plasma membrane.

Report

(4 results)
  • 1992 Annual Research Report   Final Research Report Summary
  • 1991 Annual Research Report
  • 1990 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Higashihara M.et al.: "The effect of low-density lipoprotein on platelet function" Acta Haematol.Jpn.53. 1630-1638 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 東原 正明他: "アポE-rich HDLと血小板凝集能" Therapeutic Research. 11. 3307-3312 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihara M.et al.: "The role of apoE in ingibitory effects of apo-E rich HDL on platelet function." FEBS Letter. 282. 82-86 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] 苅家 利承他: "血小板膜の脂質代謝" 臨床病理. 91(特集). 180-193 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihara M.et al.: "Inhibition of platelet function by high-density lipoprotein from a patient with apolipoprotein E deficiency" Biochem.Biophys.Res.Commun.181. 1331-1336 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higasihara M, Miura N, Kawakami H and Teramoto T.: "The effect of low-density lipoprotein on platelet function" Acta Haematol. Jpn.53. 1630-1638 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihra M and Teramoto T.: "ApoE-rich HDL and platelet aggregation" Therapeutic Research. 11. 3307-3312 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihara M, Kinoshita M, Teramoto T, Kume S and Kurokawa K.: "The role of apoE in inhibitory effects of apo-E rich HDL on platelet function." FEBS Letter. 282. 82-86 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Kariya T, Kawasaki S, Higashihara M, Ozaki Y and Kume S.: "Lipid metabolism in platelet membrane" Jpn. J.Clin.Pathol.91(suppl). 180-193 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihara M, Kinoshita M, Kume S, Teramoto T and Kurokawa K.: "Inhibition of platelet function by high-density lipoprotein from a patient with apolipoprotein E deficiency" Biochem. Biophys. Res. Commun.181. 1331-1336 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1992 Final Research Report Summary
  • [Publications] Higashihara M. et al.: "The effect of low-density lipoprotein on platelet function" Acta Haematol.Jpn.53. 1630-1638 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] 東原 正明 他: "アポE-rich HDLと血小板凝集能" Therapeutic Research. 11. 3307-3312 (1990)

    • Related Report
      1992 Annual Research Report
  • [Publications] Higashihara M. et al.: "The role of apoE in inhibitory effects of apo-E rich HDL on platelet function." FEBS Letter. 282. 82-86 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] 苅家 利承 他: "血小板膜の脂質代謝" 臨床病理. 91(特集). 180-193 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Higashihara M. et al.: "Inhibition of platelet function by high-density lipoprotein from a patient with apolipoprotein E deficiency" Biochem.Biophys.Res.Commun.181. 1331-1336 (1991)

    • Related Report
      1992 Annual Research Report
  • [Publications] Higashihara M.et al.: "The effect of lowーdensity lipoprotein on platelet function" Acta Haematol.Jpn.53. 1630-1638 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] 東原 正明 他: "アポEーrich HDLと血小板凝集能" Therapeutic Research. 11. 3307-3312 (1990)

    • Related Report
      1991 Annual Research Report
  • [Publications] Higashihara M.et al.: "The role of apoE in inhibitory effects of apoーE rich HDL on platelet function." FEBS Letter. 282. 82-86 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 苅家 利承 他: "血小板膜の脂質代謝" 臨床病理. 91(特集). 180-193 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Higashihara M.et al.: "Inhibition of platelet function by highーdensity lipoprotein from a patient with apolipoprotein E deficiency" Biochem.Biophys.Res.Commun.(1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Higashihara M.,et al.: "The effect of lowーdensity lipoprotein on platelet function." ACTA Haematol.Jpn.53. 1630-1638 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Higashihara M.,et al.: "The role of apo E in inhibitory effects of apo Eーrich HDL on platelet function." FEBS Letter. (1991)

    • Related Report
      1990 Annual Research Report

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

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