Shear-induced interaction of platelets with von Willebrand factor results in glycoprotein Ib shedding

Physiol 297: H2128 –H2135, 2009. First published October 9, 2009; doi:10.1152/ajpheart.00107.2009.—Shear-induced platelet ad-hesion through the interaction of glycoprotein (GP) Ib with von Wille-brand factor (VWF) exposed at the injured vessel wall or atherosclerotic plaque rupture is a prerequisite for the physiological hemostatic process or pathological thrombus formation in stenosed arteries. Here we show that shear-induced interaction of platelets with immobilized VWF results in GPIb ectodomain shedding. Washed platelets were exposed to VWF-coated glass capillary or cone-and-plate viscometer at different shear rates, and GPIb ectodomain was shed from platelets, while a small mass of GPIb COOH-terminal peptide, 17 kDa, was increased cor-respondingly. The extent of GPIb shedding was enhanced with the concentration of immobilized VWF and the time duration of constant shear stress, whereas it was obviously reduced with the decreased number of adherent platelets. Pretreatment of platelets with membrane-permeabl