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Proteomic Analysis of Extracellular Vesicle Cargoes Mirror the Cardioprotective Effects of Rivaroxaban in Patients with Venous Thromboembolism
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  • Luisa Weiss,
  • Wido Uhrig,
  • Sarah Kelliher,
  • Paulina Szklanna,
  • Tadhg Prendiville,
  • Shane P. Comer,
  • Osasere Edebiri,
  • Karl Egan,
  • Áine Lennon,
  • Barry Kevane,
  • Séan Murphy,
  • Fionnuala Ní Áinle,
  • Patricia B Maguire
Luisa Weiss
University College Dublin
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Wido Uhrig
University College Dublin
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Sarah Kelliher
University College Dublin
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Paulina Szklanna
University College Dublin
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Tadhg Prendiville
Mater Misericordiae University Hospital
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Shane P. Comer
University College Dublin
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Osasere Edebiri
Mater Misericordiae University Hospital
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Karl Egan
University College Dublin
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Áine Lennon
Mater Misericordiae University Hospital
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Barry Kevane
University College Dublin
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Séan Murphy
Mater Misericordiae University Hospital
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Fionnuala Ní Áinle
University College Dublin
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Patricia B Maguire
University College Dublin

Corresponding Author:patricia.maguire@ucd.ie

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Abstract

Venous Thromboembolism (VTE) remains a significant cause of morbidity and mortality worldwide. Rivaroxaban, a direct oral factor Xa inhibitor, mediates anti-inflammatory and cardiovascular-protective effects besides its well-established anticoagulant properties; yet, these remain poorly characterized. Extracellular vesicles (EVs) are considered proinflammatory messengers regulating a myriad of (patho)physiological processes and may be highly relevant to the pathophysiology of VTE. The effects of Rivaroxaban on circulating EVs in VTE patients remain unknown. We have established that differential EV biosignatures are found in patients with non-valvular atrial fibrillation anticoagulated with Rivaroxaban versus warfarin. Here, we investigated whether differential proteomic profiles of circulating EVs could also be found in patients with VTE. We performed comparative label-free quantitative proteomic profiling of enriched plasma EVs from VTE patients anticoagulated with either Rivaroxaban or warfarin using a tandem mass spectrometry approach. Of the 181 quantified proteins, 6 were found to be either exclusive to, or enriched in, Rivaroxaban-treated patients. Intriguingly, these proteins form a cluster tightly involved in negative feedback regulation of inflammatory and coagulation pathways, suggesting that EV proteomic signatures may reflect both Rivaroxaban’s anti-coagulatory and anti-inflammatory potential. These findings may be of translational relevance towards characterizing the emerging anti-inflammatory and cardioprotective mechanisms associated with this therapy.
10 Feb 2023Submitted to Clinical Applications
15 Feb 2023Submission Checks Completed
15 Feb 2023Assigned to Editor
15 Feb 2023Review(s) Completed, Editorial Evaluation Pending
15 Feb 2023Reviewer(s) Assigned
12 May 2023Editorial Decision: Revise Major
07 Sep 2023Review(s) Completed, Editorial Evaluation Pending
07 Sep 20231st Revision Received
08 Sep 2023Reviewer(s) Assigned