Hemostatic effects of phospholipid vesicles carrying fibrinogen γ chain dodecapeptide in vitro and in vivo

Yosuke Okamura, Ippei Maekawa, Yuji Teramura, Hitomi Maruyama, Makoto Handa, Yasuo Ikeda, Shinji Takeoka

    Research output: Contribution to journalArticle

    45 Citations (Scopus)

    Abstract

    We studied prototypes of platelet substitutes that bear on their surface a dodecapeptide, HHLG-GAKQAGDV (H12). The peptide is a fibrinogen γ chain carboxy-terminal sequence (γ400-411) and recognizes specifically the active form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a phospholipid vesicle with an average diameter of 220 nm to prepare H12-PEG-vesicles. The half-life of the H12-PEG-vesicles was significantly prolonged by PEG modification, and the ability of H12 on the surface of the vesicle to recognize GPIIb/IIIa was maintained even though the surface was modified with PEG chains. The H12-PEG-veiscles enhanced the in vitro thrombus formation of platelets that were adhering to a collagen-immobilized plate, when thrombocytopenia-imitation blood was passed over the plate. Based on the flow cytometric analyses of PAC-1 binding and P-selectin expression, the H12-PEG-vesicles were shown not to cause platelet activation. Furthermore, the H12-PEG-vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic rats. It was confirmed that the H12-PEG-vesicles had a hemostatic effect and may be a suitable candidate for an alternative to human platelet concentrates transfused into thrombocytopenic patients.

    Original languageEnglish
    Pages (from-to)1589-1596
    Number of pages8
    JournalBioconjugate Chemistry
    Volume16
    Issue number6
    DOIs
    Publication statusPublished - 2005 Nov

    Fingerprint

    Phospholipids
    Hemostatics
    Fibrinogen
    Polyethylene glycols
    Blood Platelets
    Platelets
    Platelet Glycoprotein GPIIb-IIIa Complex
    Bleeding Time
    P-Selectin
    Ethylene Glycol
    Platelet Activation
    Thrombocytopenia
    Half-Life
    Tail
    Thrombosis
    Collagen
    Peptides
    In Vitro Techniques
    Glycoproteins
    Rats

    ASJC Scopus subject areas

    • Chemistry(all)
    • Organic Chemistry
    • Clinical Biochemistry
    • Biochemistry, Genetics and Molecular Biology(all)
    • Biochemistry

    Cite this

    Hemostatic effects of phospholipid vesicles carrying fibrinogen γ chain dodecapeptide in vitro and in vivo. / Okamura, Yosuke; Maekawa, Ippei; Teramura, Yuji; Maruyama, Hitomi; Handa, Makoto; Ikeda, Yasuo; Takeoka, Shinji.

    In: Bioconjugate Chemistry, Vol. 16, No. 6, 11.2005, p. 1589-1596.

    Research output: Contribution to journalArticle

    Okamura, Yosuke ; Maekawa, Ippei ; Teramura, Yuji ; Maruyama, Hitomi ; Handa, Makoto ; Ikeda, Yasuo ; Takeoka, Shinji. / Hemostatic effects of phospholipid vesicles carrying fibrinogen γ chain dodecapeptide in vitro and in vivo. In: Bioconjugate Chemistry. 2005 ; Vol. 16, No. 6. pp. 1589-1596.
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