title: Properties of soluble glycoprotein VI, a potential platelet activation biomarker.
abstract: Glycoprotein VI (GPVI) plays a critical role in the platelet response to collagen. Clinical studies suggest that the plasma level of soluble GPVI (sGPVI) is a highly specific and useful platelet activation marker. However, many properties of sGPVI have not been fully characterized, such as its sensitivity in detecting platelet activation and its elimination rate from the blood. In this study we established a sandwich enzyme-linked immunosorbent assay for human sGPVI, which cross-reacts to cynomolgus monkey sGPVI, and evaluated the time course of sGPVI production in a cynomolgus monkey model of lipopolysaccharide (LPS)-induced thrombocytopenia. The sGPVI levels in this model were dramatically elevated and returned to baseline by 24 hours after LPS injection, the change was more pronounced than the existing platelet activation biomarker, soluble P-selectin (sP-selectin) levels. The elimination half-life of recombinant human sGPVI was about 2.5 hours following intravenous administration to monkeys. These results suggest that plasma sGPVI closely reflects platelet activation in the bloodstream and has a short half-life. sGPVI would be a useful biomarker for disorders marked by platelet activation and for monitoring anti-platelet therapy.
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Naitoh
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hosaka
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Motoyasu
authors.initials: M
authors.lastname: Honda
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Ogawa
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Kamon
authors.initials: K
authors.lastname: Shirakawa
authors.affiliation: a Biology Laboratory, Discovery Research, Mochida Pharmaceutical Co., LTD. , Jimba , Gotemba , Shizuoka , Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Furusako
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers; D001792:Blood Platelets / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D016415:Sequence Alignment; D013921:Thrombocytopenia / Q000097:blood / Q000378:metabolism; D013997:Time Factors
chemical_list: D015415:Biomarkers; D019007:P-Selectin; D010980:Platelet Membrane Glycoproteins; D011994:Recombinant Proteins; C098341:platelet membrane glycoprotein VI
keywords: Cynomolgus monkey; glycoprotein VI; platelets