Luka, N., South, K., Jones, R. et al. (14 more authors) (2025) The Role of the VWF/ADAMTS13 Axis in the Thromboinflammatory Response in Ischemic Stroke After SARS-CoV2 Infection. Brain and Behavior, 15 (2). e70348. ISSN 2162-3279
Abstract
Background SARS-CoV2 infections increase the risk of ischemic stroke (IS), potentially through a thromboinflammatory cascade driven by an imbalance in the ratio of Von Willebrand Factor (VWF) and a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), leading to the formation of ultra-large VWF (UL-VWF). However, the SARS-CoV2 infection's contribution to any VWF/ADAMTS13 axis imbalance and the subsequent thromboinflammatory response post-stroke remain poorly understood.
Methods We performed a detailed thromboinflammatory profile of the plasma samples from three experimental cohorts matched by age, sex, and stroke severity: non-stroke controls (n = 23), SARS-CoV2 negative IS (n = 22), and SARS-CoV2 positive IS (n = 24). SARS-CoV2 positive IS patients presented varying degrees of infection severity.
Results We observed an increase in VWF and UL-VWF and a decrease in ADAMTS13 in the SARS-CoV2 positive IS cohort, suggesting a VWF/ADAMTS13 axis imbalance. Interleukin-6 (IL-6) levels were positively correlated with VWF and negatively correlated with ADAMTS13, suggesting that IL-6 may drive this imbalance. Fibrinogen and D-Dimers were elevated in SARS-CoV2 negative IS cohort and SARS-CoV2 positive IS cohort, but D-Dimers were within the normal range, indicating no disseminated intravascular coagulation. Factor IX (FIX) was elevated in the SARS-CoV2 negative IS cohort. Tissue plasminogen activator (tPA) was elevated in the SARS-CoV2 positive IS cohort, suggesting no fibrinolysis defects. Matrix Metalloproteinase-2 (MMP-2) and soluble Intracellular Adhesion Molecule-1 (sICAM-1) were elevated in the SARS-CoV2 negative IS cohort.
Conclusions We show that SARS-CoV2 infections drive a VWF/ADAMTS13 axis imbalance, inducing an increase in tPA while decreasing FIX, MMP-2, and sICAM-1 post-stroke.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | ADAMTS13, ischemic stroke and thromboinflammation, SARS-CoV2, VWF |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 04 Feb 2025 11:46 |
Last Modified: | 06 Mar 2025 12:00 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/brb3.70348 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:222861 |