Journal article
Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke
Blood advances, Vol.9(6), pp.1330-1341
03/25/2025
DOI: 10.1182/bloodadvances.2024014622
PMCID: PMC11950970
PMID: 39787593
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 axis in patients with RTIs, including COVID-19. 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 S. aureus (on days 0, 2, and 5) or mouse-adapted SARS-CoV-2 (on day 0) and subjected to transient (30 or 45 min) 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 post-reperfusion. In SARS-CoV-2-infected mice, infarct volumes and functional outcomes (Bederson score) were assessed on day 1 post-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 IL-6, CXCL1, and MCP-1, which was associated with larger infarcts and worse functional outcomes (P<0.05 vs. mock-infection). S. aureus- or SARS-CoV-2-infected Vwf -/- mice exhibited reduced infarcts and improved functional outcomes, while infected Adamts13-/- mice displayed greater stroke severity (P<0.05 vs. control). In the models of RTI preceding stroke, VWF contributes to stroke severity, while ADAMTS13 is protective.
Details
- Title: Subtitle
- Imbalanced VWF-ADAMTS13 axis contributes to the detrimental impact of a preceding respiratory tract infection on stroke
- Creators
- Rakesh B Patel - University of Iowa, Internal MedicineAbhishek B Jha - University of IowaAbhishek K Verma - University of IowaAditi Jain - University of Iowa, Internal MedicineSaurabh Saini - University of Iowa, Internal MedicineJoshua Muia - Versiti Blood Center of WisconsinPrajwal Gurung - University of IowaStanley Perlman - University of IowaIvan Budnik - University of IowaAnil Chauhan - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Blood advances, Vol.9(6), pp.1330-1341
- DOI
- 10.1182/bloodadvances.2024014622
- PMID
- 39787593
- PMCID
- PMC11950970
- NLM abbreviation
- Blood Adv
- ISSN
- 2473-9537
- eISSN
- 2473-9537
- Publisher
- ELSEVIER; AMSTERDAM
- Grant note
- National Institutes of HealthNational Heart, Lung, and Blood Institute: R35HL139926 National Institute of Neurological Disorders and Stroke: U01NS130587 National Institutes of Health, National Institute of General Medical Sciences: R35GM142936 American Heart Association: 24POST1195275
The A.K.C. laboratory is supported by grants from the National Institutes of Health, including the National Heart, Lung, and Blood Institute (grant R35HL139926) and the National Institute of Neurological Disorders and Stroke (grant U01NS130587). J.M. is supported by a National Institutes of Health, National Institute of General Medical Sciences grant (grant R35GM142936). R.B.P. is supported by the American Heart Association postdoctoral award (24POST1195275).
- Language
- English
- Electronic publication date
- 01/09/2025
- Date published
- 03/25/2025
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics); Internal Medicine
- Record Identifier
- 9984772278102771
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