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

Alice Apostoli, Valentina Bianchi, Nina Bono, Annalisa Dimasi, Kaitlyn R. Ammann, Yana Roka Moiia, Andrea Montisci, Jawaad Sheriff, Danny Bluestein, Gianfranco B. Fiore, Federico Pappalardo, Gabriele Candiani, Alberto Redaelli, Marvin J. Slepian, Filippo Consolo

Research output: Contribution to journalArticle

1 Scopus citations

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/cm2, 10 minutes) via a hemodynamic shearing device. ECs were activated via exposure to inflammatory tumor necrosis factor-α (TNF-α 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/cm2 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-α concentration: thrombin generation of 70 dynes/cm2 shear-activated platelets was 2.6-fold higher after exposure and adhesion to 100 ng/ml TNF-α‒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.

Original languageEnglish (US)
Pages (from-to)658-667
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume38
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Endothelial cells
  • inflammation
  • platelets
  • shear stress
  • thrombosis
  • ventricular assist device

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Apostoli, A., Bianchi, V., Bono, N., Dimasi, A., Ammann, K. R., Moiia, Y. R., Montisci, A., Sheriff, J., Bluestein, D., Fiore, G. B., Pappalardo, F., Candiani, G., Redaelli, A., Slepian, M. J., & Consolo, F. (2019). Prothrombotic activity of cytokine-activated endothelial cells and shear-activated platelets in the setting of ventricular assist device support. Journal of Heart and Lung Transplantation, 38(6), 658-667. https://doi.org/10.1016/j.healun.2019.02.009