Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity

Furihata, K; Clemetson, KJ; Deguchi, H; Kunicki, TJ (2001). Variation in human platelet glycoprotein VI content modulates glycoprotein VI-specific prothrombinase activity. Arteriosclerosis, thrombosis, and vascular biology, 21(11), pp. 1857-63. Philadelphia, Pa.: Lippincott Williams & Wilkins 10.1161/hq1001.096643

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- Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen that figures prominently in signal transduction. An addition to binding to type I and III collagens, GPVI is also bound specifically by collagen-related peptide and convulxin (CVX), a snake venom protein. We developed a quantitative assay of platelet GPVI in which biotin-conjugated CVX binds selectively to GPVI in separated total platelet proteins by a ligand blot procedure. Using this approach, we have documented a 5-fold range in platelet GPVI content among 23 normal healthy subjects. In addition, we have determined that CVX-induced or collagen-related peptide-induced prothrombinase activity is directly proportional to the platelet content of GPVI. A statistically significant correlation was observed at 2 CVX concentrations: 14.7 ng/mL (R(2)=0.854 and P<0.001, n=11) and 22 ng/mL (R(2)=0.776 and P<0.001, n=12). In previous studies, we established a similar range of expression of the integrin collagen receptor alpha(2)beta(1) on platelets of normal subjects. Among 15 donors, there is a direct correlation between platelet alpha(2)beta(1) density and GPVI content (R(2)=0.475 and P=0.004). In view of the well-documented association of GPVI with platelet procoagulant activity, this study suggests that the variation in GPVI content is a potential risk factor that may predispose individuals to hemorrhagic or thromboembolic disorders.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Clemetson, Kenneth John

ISSN:

1079-5642

ISBN:

11701478

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:52

Last Modified:

04 May 2014 23:15

Publisher DOI:

10.1161/hq1001.096643

PubMed ID:

11701478

Web of Science ID:

000172206900026

URI:

https://boris.unibe.ch/id/eprint/22197 (FactScience: 32248)

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