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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2001;21:1857.)
© 2001 American Heart Association, Inc.

Thrombosis

Variation in Human Platelet Glycoprotein VI Content Modulates Glycoprotein VI–Specific Prothrombinase Activity

Kenichi Furihata; Kenneth J. Clemetson; Hiroshi Deguchi; Thomas J. Kunicki

From the Roon Research Center for Arteriosclerosis and Thrombosis (K.F., H.D., T.J.K.), Division of Experimental Hemostasis and Thrombosis of the Department of Molecular and Experimental Medicine, and the Department of Vascular Biology (T.J.K.), The Scripps Research Institute, La Jolla, Calif, and the Theodor Kocher Institute (K.J.C.), University of Berne, Berne, Switzerland.

Correspondence to Thomas J. Kunicki, PhD, The Scripps Research Institute, Department of Molecular and Experimental Medicine, MEM-150, 10550 North Torrey Pines Rd, La Jolla, CA 92037. E-mail tomk{at}scripps.edu

Abstract—— 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 (R²=0.854 and P<0.001, n=11) and 22 ng/mL (R²=0.776 and P<0.001, n=12). In previous studies, we established a similar range of expression of the integrin collagen receptor ₂ß₁ on platelets of normal subjects. Among 15 donors, there is a direct correlation between platelet ₂ß₁ density and GPVI content (R²=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.

Key Words: platelets • glycoprotein VI • ₂ß₁ complex • polymorphism • prothrombinase

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