caa a22 4500 606234764 CHVBK 20210128101239.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s11010-015-2515-y doi (NATIONALLICENCE)springer-10.1007/s11010-015-2515-y Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress [Elektronische Daten] [Zengsheng Chen, Nandan Mondal, Jun Ding, Steven Koenig, Mark Slaughter, Bartley Griffith, Zhongjun Wu] The purpose of this study was to investigate the influence of non-physiological high shear stress on activation and shedding of platelet GP IIb/IIIa receptors. The healthy donor blood was exposed to three levels of high shear stresses (25, 75, 125Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5s), created by a specific blood shearing system. The activation and shedding of the platelet GPIIb/IIIa were analyzed using flow cytometry and enzyme-linked immunosorbent assay. In addition, platelet P-selectin expression of sheared blood, which is a marker for activated platelets, was also analyzed. The results from the present study showed that the number of activated platelets, as indicated by the surface GPIIb/IIIa activation and P-selectin expression, increased with increasing the shear stress level and exposure time. However, the mean fluorescence of GPIIb/IIIa on the platelet surface, decreased with increasing the shear stress level and exposure time. The reduction of GPIIb/IIIa on the platelet surface was further proved by the reduction of further activated platelet GPIIb/IIIa surface expression induced by ADP and the increase in GPIIb/IIIa concentration in microparticle-free plasma with increasing the applied shear stress and exposure time. It is clear that non-physiological shear stress induce a paradoxical phenomenon, in which both activation and shedding of the GPIIb/IIIa on the platelet surface occur simultaneously. This study may offer a new perspective to explain the reason of both increased thrombosis and bleeding events in patients implanted with high shear blood-contacting medical devices. Springer Science+Business Media New York, 2015 Glycoprotein IIb/IIIa (Integrin αIIb/β3) nationallicence Blood-contacting medical devices nationallicence Non-physiological shear stress nationallicence Shear-induced hemostatic dysfunction nationallicence Shear-induced platelet activation nationallicence Chen Zengsheng Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Mondal Nandan Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Ding Jun Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Koenig Steven Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Slaughter Mark Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Griffith Bartley Department of Surgery, School of Medicine, University of Maryland, 21201, Baltimore, MD, USA aut Wu Zhongjun Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 93-101 0300-8177 409:1-2<93 2015 409 11010 https://doi.org/10.1007/s11010-015-2515-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2515-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chen Zengsheng Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Mondal Nandan Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Ding Jun Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Koenig Steven Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Slaughter Mark Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 700 1- Griffith Bartley Department of Surgery, School of Medicine, University of Maryland, 21201, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Wu Zhongjun Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, 40202, Louisville, KY, USA aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 409/1-2(2015-11-01), 93-101 0300-8177 409:1-2<93 2015 409 11010