Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke

By Internal Medicine at Iowa
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Article: Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke

Authors: Rakesh B Patel, Abhishek B Jha, Aditi Jain, Abhishek K Verma, Saurabh Saini, Joshua Muia, Prajwal Gurung, Stanley Perlman, Ivan Budnik, Anil K Chauhan

Journal: Blood Adv. 2025 Mar 25;9(6):1330-1341

Abstract:
Respiratory tract infections (RTIs) caused by bacteria or viruses are associated with stroke severity. Recent studies have revealed an imbalance in the von Willebrand factor (VWF)-ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motifs 13) axis in patients with RTIs, including coronavirus disease 2019. We examined whether this imbalance contributes to RTI-mediated stroke severity. Wild-type (WT), Vwf-/-, or Adamts13-/- mice with respective littermate controls (Vwf+/+ or Adamts13+/+) were infected intranasally with sublethal doses of Staphylococcus aureus (on days 0, 2, and 5) or mouse-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; on day 0) and subjected to transient (30 or 45 minutes) cerebral ischemia followed by reperfusion. In S aureus-infected mice, infarct volumes were assessed on day 2 and functional outcomes on weeks 1 and 4 after reperfusion. In SARS-CoV-2-infected mice, infarct volumes and functional outcomes (Bederson score) were assessed on day 1 after reperfusion. We demonstrated that S aureus or SARS-CoV-2 RTI was accompanied by an imbalance in the VWF-ADAMTS13 axis and an increase in plasma levels of interleukin-6, C-X-C motif chemokine ligand 1, and monocyte chemoattractant protein-1, which was associated with larger infarcts and worse functional outcomes (P < .05 vs mock infection). S aureus- or SARS-CoV-2-infected Vwf-/- mice exhibited reduced infarcts and improved functional outcomes, whereas infected Adamts13-/- mice displayed greater stroke severity (P < .05 vs control). In the models of RTI preceding stroke, VWF contributes to stroke severity, whereas ADAMTS13 is protective.

Link to journal online: https://ashpublications.org/bloodadvances/article/9/6/1330/534991/Imbalanced-VWF-ADAMTS13-axis-contributes-to-the

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