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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Profiling of extracellular vesicles and thrombo-inflammatory biomarkers in patients with pulmonary embolism Prakasha Kempaiah1, Mira Nigudkar1, Martin Lundy1, Fahika Siddiqui1, Chongyu Zhang1, Bulent Kantarcioglu1, Debra Hoppensteadt1, Jeanine Walenga1, Thao Doan2, Jawed Fareed1, Amir Darki3, W.Keith Jones 1. 1Loyola University Stritch School of Medicine, Chicago, IL, USA.2AbbVie, North Chicago, Illinois, USA, Chicago, IL, USA.3Division of Cardiovascular Disease and Department of Internal Medicine, Loyola University Chicago, Chicago, IL, USA |
Abstract
Introduction: Pulmonary embolism (PE) is a life-threatening cardiovascular condition characterized by the obstruction of pulmonary arteries, from deep vein thrombosis (DVT). Given the high prevalence and complexity of PE, understanding cellular changes, including extracellular vesicles (EVs) and thrombo-inflammatory markers, may enhance diagnostic accuracy. EVs have emerged as promising cellular biomarkers that carry molecular signatures of the underlying body’s response to cellular stress. EVs are derived from the endosomal reticulum and carry proteins, lipids, and nucleic acids. Importantly, EVs can reflect the molecular state of their producer cells and simultaneously modulate multiple biological processes in recipient cells, including fibrinolysis, endothelial activation and inflammatory pathways. Integrating EV profiling with circulating plasma biomarkers may provide a more refined molecular characterization of the pathophysiology of PE, offering insight into potential pathways for improved diagnostic and prognostic strategies. Methods: Plasma samples from 65 patients diagnosed with acute PE and managed by the Pulmonary Embolism Response Team (PERT) were collected under a pre-approved IRB protocol (LU#2094572) at Loyola University Medical Center. Controls were normal human plasma samples from 15 individuals. Expression of fibrinolytic (D-dimer, PAI-1, tPA) and endothelial (vWF, Angiopoietin-2, nitrotyrosine) biomarkers was quantified using Enzyme-Linked Immunosorbent Assays. Pro-inflammatory cytokine TNFα was measured using Chemiluminescence Biochip Array from Randox Technology. EVs were isolated from plasma via modified size exclusion chromatography. Vesicle size and concentration were measured using nanoparticle tracking analysis (NTA) with Nanosight NS300. Results: Plasma biomarker profiling revealed robust differences between PE patients and normal controls. Expression of fibrinolytic biomarkers was significantly elevated in PE patients, including D-dimer (p<0.0001), PAI-1 (p<0.0001), and tPA (p<0.0001). Markers of endothelial dysfunction were also increased, including vWF (p<0.0001), Angiopoietin-2 (p<0.0001), and nitrotyrosine (p=0.0033). Similarly, pro-inflammatory TNFα was elevated (p=0.0084). Amongst all biomarkers, those related to fibrinolytic dysfunction exhibited the greatest fold increases in patients; D-dimer showed the highest fold change (10.5x), followed by PAI-1 (3.6x) and tPA (3.1x). Preliminary EV profiling further differentiated PE patients from normal individuals. EVs isolated from PE patients (n=31) displayed a larger diameter (median: 179.0, IQR: 155.1-202.7 nm) compared with those from controls (median: 123.5, IQR: 112.8-136.8 nm; n=15) (p<0.0001) (Fig. 1). Interestingly, despite their increased size, EVs from PE patients exhibited a nonsignificant trend to reduced particle concentration (median: 2.97 × 10¹⁰, IQR: 1.49 × 10¹⁰-3.99× 10¹⁰ particles/mL) relative to controls (median: 4.10 × 10¹⁰, IQR: 1.58 × 10¹⁰-5.37 × 10¹⁰ particles/mL) (p=0.1978) (Fig. 2). Conclusion: This study demonstrates significant dysregulation of fibrinolytic, endothelial, and inflammatory mediators in acute PE, with fibrinolysis-related markers showing the greatest elevations. Characterization of EVs in PE patients reveals a distinct alterations in size and a trend towards reduced concentration, highlighting thrombotic stress and vascular disruption. This aberration may reflect altered EV production or changes in the molecular composition of circulating EVs. Together, these findings support integration of biomarker profiling with EV analysis as a novel diagnostic and prognostic tool in thromboembolic disease. Future studies will focus on molecular characterization of EVs and identify specific microRNAs associated with the severity of pulmonary embolism.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.