title: Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress.
abstract: 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, 125 Pa) from the physiological to non-physiological status with three short exposure time (0.05, 0.5, 1.5 s), 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.
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA.|Department of Engineering Mechanics, School of Aerospace, Tsinghua University, Beijing, 100084, China.
authors.forename: Zengsheng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA.
authors.forename: Nandan K
authors.initials: NK
authors.lastname: Mondal
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA.|Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore, MD, 21250, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Koenig
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Slaughter
authors.affiliation: Department of Surgery, School of Medicine, University of Maryland, Baltimore, MD, 21201, USA.
authors.forename: Bartley P
authors.initials: BP
authors.lastname: Griffith
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Cardiovascular Innovation Institute, University of Louisville School of Medicine, Room 410, 302 E. Muhammad Ali Blvd, Louisville, KY, 40202, USA. zhongjun.wu@louisville.edu.
authors.forename: Zhongjun J
authors.initials: ZJ
authors.lastname: Wu
mesh_terms: D001777:Blood Coagulation; D001792:Blood Platelets / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006470:Hemorrhage / Q000473:pathology; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000378:metabolism; D015539:Platelet Activation / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019736:Prostheses and Implants / Q000009:adverse effects*; D013314:Stress, Mechanical; D013312:Stress, Physiological / Q000502:physiology*; D013927:Thrombosis / Q000473:pathology
chemical_list: D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Blood-contacting medical devices; Glycoprotein IIb/IIIa (Integrin αIIb/β3); Non-physiological shear stress; Shear-induced hemostatic dysfunction; Shear-induced platelet activation