Epinephrine and shear stress synergistically induce platelet aggregation via a mechanism that partially bypasses vWF-Gp Ib interactions |
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| Affiliation: | 1. Cox Laboratory for Biomedical Engineering, Rice University, Houston, TX, 77251, USA;2. Medical Services, Houston VA Medical Center and Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;1. Department of medicine, Medical University of South Carolina, Charleston, SC, USA;3. From the Storr Liver Centre, Westmead Millennium Institute, University of Sydney at Westmead Hospital, Westmead, New South Wales 2145, Australia and;4. the Department of Medicine, the University of Hong Kong, Hong Kong, China;1. University of Florida Health, Department of Surgery and Sepsis and Critical Illness Research Center, Gainesville, FL, USA;2. University of Florida, College of Medicine, Gainesville, FL, USA;1. Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy;2. Regenerative Medicine and Fibrosis Group, Institute for Liver and Digestive Health, University College London, Royal Free Campus London, United Kingdom;3. Sheila Sherlock Liver Centre, Royal Free Hospital, London, United Kingdom;4. Department of Cellular Pathology, UCL Medical School, Royal Free Campus, United Kingdom;5. Institute for Liver and Digestive Health, Division of Medicine, University College London, London, United Kingdom;6. Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, Careggi University Hospital, Florence, Italy;3. Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612;4. Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois 60612,;5. the Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, and;4. the Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois 60612;1. Institute of Fundamental and Clinical Immunology, Novosibirsk, Russia;2. The Federal Research Center Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia;3. Novosibirsk State Medical University, Novosibirsk, Russia;4. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia |
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| Abstract: | Elevated shear stress levels in pathologically stenosed vessels induce platelet activation and aggregation, and may play a role in the pathogenesis of arterial disease. Increased plasma catecholamine concentrations have also been implicated in the onset of acute coronary ischemic syndromes. This study was designed to examine the synergistic interaction of shear stress and epinephrine in the activation of platelets. Platelets (in PRP) sheared at 60 dyn/cm2 showed little or no aggregation unless pretreated with epinephrine. Pretreatment with 250 nM epinephrine followed by shear at 60 dyn/cm2 induced >60% platelet aggregation. The specific α2-adrenergic receptor antagonist yohimbine inhibited the synergistic aggregation, as did the ADP scavenging system phosphocreatine/creatine phosphokinase, indicating a three-way synergism with ADP. Chemical or monoclonal antibody blockade of von Willebrand factor (vWF) interactions with either platelet glycoprotein (Gp) Ib or Gp IIb/IIIa completely inhibited platelet aggregation induced by activating levels of shear stress alone. However, the combination of epinephrine and shear stress induced platelet aggregation that was blocked by 10E5, a monoclonal antibody that inhibits vWF binding to Gp IIb/IIIa, but not by aurin tricarboxylic acid or the monoclonal antibody 6D1, both of which inhibit vWF binding to Gp Ib. Synergistic platelet aggregation in response to epinephrine and shear stress was observed in washed platelets, platelet-rich plasma and whole blood in vitro, and also ex vivo following exercise to elevate endogenous levels of catecholamines. These results indicate that epinephrine synergizes with shear stress to induce platelet aggregation. This synergistic response requires functional Gp IIb/IIIa complexes, but is at least partially independent of vWF-Gp Ib interactions. |
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