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Hyperaggregability of platelets in familiar hypercholesterolemic patients and its treatment with polyunsaturated fatty acids in fish oil

Research Project

Project/Area Number 01570626
Research Category

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

Allocation TypeSingle-year Grants
Research Field 内分泌・代謝学
Research InstitutionChiba University

Principal Investigator

HIRAI Aizan  Chiba University, Department of Medicine Assistant, 医学部附属病院, 助手 (10189813)

Co-Investigator(Kenkyū-buntansha) TAMURA Yasushi  Chiba University, Department of Medicine Associate Professor, 医学部, 助教授 (90009671)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1990: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1989: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsEPA / 11-dehydro-TXB2 / 2, 3-dinor-6-ketoPGF_1 alpha / Platelets / 魚脂多価不飽和脂肪酸 / EPA / 家族性高コレステロ-ル血症 / プロスタサイクリン / トロンボキサンA_2 / 多価不飽和脂肪酸 / エイコサペンタエン酸 / ドコサヘキサエン酸
Research Abstract

The effect of changes in platelet membrane cholesterol content on thromboxane A_2(TXA_2)-induced platelet activation was studied. Concentrations of 9,11-epithio-11,12-methano-TXA_2 (STA_2), a stable analogue of TXA_2 which can cause half-maximal aggregation and release of [^<14>C] serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA_2-induced increase in cytosolic calcium concentration and [^<32>P] phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site for SQ29548 was signifi-cantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the effect of changes in platelet membrane cholesterol content on thromboxane A_2(TXA_2)-induced platelet activation was studied. Concentrations of 9,11-epithio-11,12-methano-TXA_2 (STA_2), a stable analogue of TXA_2 which can cause half-maximal aggregation and release of [^<14>] serotonin in cholesterol-rich platelets were significantly lower than those in cholesterol-normal platelets. STA_2-induced increase in cytosolic calcium concentration and [^<32>P] phosphatidic acid formation in cholesterol-rich platelets were significantly greater than those in cholesterol-normal platelets. The maximal concentration of binding site for SQ29548 was significantly increased in cholesterol-rich platelets compared with cholesterol-normal platelets, while the equilibrium dissociation rate constant for SQ29548 did not differ between cholesterol-rich and cholesterol-normal platelets. The present study suggested that sensitivity to TXA2 was increased by the incorporation of cholesterol into platelet membrane and that the cause of hyper-sensitivity to TXA_2 in cholesterol-rich platelets may be partly explained by an increase in binding capacity for TXA_2.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] 山本 恭平、平井 愛山、森尾 比呂志、田村 泰、吉田 尚: "尿中11ーデヒドロートロンボキサンB_2のラジオイムアッセイ法の検討" ホルモンと臨床.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T.Tomizuka,K.Yamamoto,A.Hirai Y.Tamura and S.Yoshida: "Hypersensivity to thromboxane A_2 in cholesterolーrich human platelets." Thrombosis and Haemostasis. 64(4). 594-599 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] T. Tomizuka, K. Yamamoto, A. Hirai, Y. Tamura and S. Yoshida: "Hypersensivity to thromboxane A_2 in cholesterol-rich human platelets." Thrombosis and Haemostasis. 64 (4). 594-599 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Kyohei Yamamoto, Aizan Hirai, Hiroshi Morio, Yasushi Tamura and Sho Yoshida: "Radioimmunoassay of 11-dehydro-thromboxane B_2 in human urine."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 山本 恭平、平井 愛山、森尾 比呂志、田村 泰、吉田 尚: "尿中11ーデヒドロ-トロンボキサンB_2のラジオイムノアッセイ法の検討" ホルモンと臨床.

    • Related Report
      1990 Annual Research Report
  • [Publications] T.Tomizuka,K.Yamamoto,A.Hirai,Y.Tamura and S.Yoshida: "Hypersensivity to thromboxane A_2 in cholesterolーrich human platelets." 64(4). 594-599 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] A.Hirai,T.Terano,Y.Tamura and S.Yoshida: "Eicosapentaenoic acid and adult disease in Japan-epidemiological and clinical aspects." J.Internal Medicine. 225. 69-75 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] T.Tomizuka,K.Yamamoto,A.Hirai,Y.Tamura and S.Yoshida: "Hypersensitivity to thromboxane A_2 in cholesterol-rich human platelets." Thrombosis and Haemostasis(under submission).

    • Related Report
      1989 Annual Research Report
  • [Publications] 平井愛山,田村泰: "ビタミンハンドブック,No.5,“ビタミンと医学"" 65-68 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] A.Hirai,T.Terano,H.Saito,and Y.Tamura: "Current Topics in Nutrition and Disease,Vol.22,Ed.by G.A.Spiller and J.Scala," Alan R.Liss,Inc.,New York,229-252

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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