Faculty Collaboration Database

Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke. Blood Adv 2025 Mar 25;9(6):1330-1341

Date

01/09/2025

Pubmed ID

39787593

Pubmed Central ID

PMC11950970

DOI

10.1182/bloodadvances.2024014622

Scopus ID

2-s2.0-105000173792 (requires institutional sign-in at Scopus site)   2 Citations

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.

Author List

Patel RB, Jha AB, Jain A, Verma AK, Saini S, Muia J, Gurung P, Perlman S, Budnik I, Chauhan AK

Author

Joshua Muia PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

ADAMTS13 Protein
Animals
Disease Models, Animal
Humans
Male
Mice
Mice, Knockout
Respiratory Tract Infections
Staphylococcal Infections
Staphylococcus aureus
Stroke
von Willebrand Factor