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    Prothrombotic activity of cytokine-activated endothelial cells and shear-activated platelets in the setting of ventricular assist device support

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    JHLT-D-18-00693R2.pdf
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    Description:
    Final Accepted Manuscript
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    Author
    Apostoli, Alice
    Bianchi, Valentina
    Bono, Nina
    Dimasi, Annalisa
    Ammann, Kaitlyn R
    Moiia, Yana Roka
    Montisci, Andrea
    Sheriff, Jawaad
    Bluestein, Danny
    Fiore, Gianfranco B
    Pappalardo, Federico
    Candiani, Gabriele
    Redaelli, Alberto cc
    Slepian, Marvin J
    Consolo, Filippo
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    Affiliation
    Univ Arizona, Dept Biomed Engn
    Issue Date
    2019-06-01
    Keywords
    Endothelial cells
    inflammation
    platelets
    shear stress
    thrombosis
    ventricular assist device
    
    Metadata
    Show full item record
    Publisher
    ELSEVIER SCIENCE INC
    Citation
    Apostoli, A., Bianchi, V., Bono, N., Dimasi, A., Ammann, K. R., Moiia, Y. R., ... & Pappalardo, F. (2019). Prothrombotic activity of cytokine-activated endothelial cells and shear-activated platelets in the setting of ventricular assist device support. The Journal of Heart and Lung Transplantation.
    Journal
    JOURNAL OF HEART AND LUNG TRANSPLANTATION
    Rights
    © 2019 International Society for Heart and Lung Transplantation. All rights reserved.
    Collection Information
    This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
    Abstract
    BACKGROUND: We systematically analyzed the synergistic effect of: (i) cytokine-mediated inflammatory activation of endothelial cells (ECs) with and (ii) shear-mediated platelet activation (SMPA) as a potential contributory mechanism to intraventricular thrombus formation in the setting of left ventricular assist device (LVAD) support. METHODS: Intact and shear-activated human platelets were exposed to non-activated and cytokine-activated ECs. To modulate the level of LVAD-related shear activation, platelets were exposed to shear stress patterns of varying magnitude (30, 50, and 70 dynes/cm(2), 10 minutes) via a hemodynamic shearing device. ECs were activated via exposure to inflammatory tumor necrosis factor-alpha (TNF-alpha 10 and 100 ng/ml, 24 hours), consistent with inflammatory activation recorded in patients on LVAD circulatory support. RESULTS: Adhesivity of shear-activated platelets to ECs was significantly higher than that of intact/unactivated platelets, regardless of the initial activation level (70 dynes/cm(2) shear-activated platelets vs intact platelets: +80%, p < 0.001). Importantly, inflammatory activation of ECs amplified platelet prothrombinase activity progressively with increasing shear stress magnitude and TNF-a concentration: thrombin generation of 70 dynes/cm(2) shear-activated platelets was 2.6-fold higher after exposure and adhesion to 100 ng/ml TNF-alpha. activated ECs (p < 0.0001). CONCLUSIONS: We demonstrated synergistic effect of SMPA and cytokine-mediated EC inflammatory activation to enhance EC. platelet adhesion and platelet prothrombotic function. These mechanisms may contribute to intraventricular thrombosis in the setting of mechanical circulatory support.
    Note
    12 month embargo; published online: 18 February 2019
    ISSN
    1557-3117
    PubMed ID
    30846234
    DOI
    10.1016/j.healun.2019.02.009
    Version
    Final accepted manuscript
    Sponsors
    Fondazione CARIPLO [2015-1044, 2016-0901]; Regione Lombardia [2016-0901]; National Institutes of Health (NIH Cardiovascular Biomedical Engineering Training Grant) [T32 HL007955]; National Institute of Biomedical Imaging and Bioengineering (Quantum Grant Award) [5U01EB012487-00]; Arizona Center for Accelerated Biomedical Innovation/Tech Launch Arizona [15-035]
    Additional Links
    https://www.jhltonline.org/article/S1053-2498(19)31390-7/fulltext
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.healun.2019.02.009
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