The Role of the VWF/ADAMTS13 Axis in the Thromboinflammatory Response in Ischemic Stroke After SARS-CoV2 Infection

IF 2.6 3区心理学 Q2 BEHAVIORAL SCIENCES Brain and Behavior Pub Date : 2025-02-19 DOI:10.1002/brb3.70348

Nadim Luka, Kieron South, Rachel Jones, Amanda J. Unsworth, Graham Coutts, Ioana-Emilia Mosneag, Mehwish Younas, Amy Bradley, Siew Yan Wong, Ellen Collins, Chloe Quigley, Sean B. Knight, Barry W. McColl, Laura McCulloch, John R. Grainger, Craig J. Smith, Stuart M. Allan

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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.

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来源期刊

Brain and Behavior BEHAVIORAL SCIENCES-NEUROSCIENCES

CiteScore

5.30

自引率

0.00%

发文量

352

审稿时长

14 weeks

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