Exacerbation of thromboinflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis
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View abstract on PubMed
Summary
This summary is machine-generated.The JAK2V617F mutation in hematopoietic cells exacerbates cerebral venous sinus thrombosis (CVST) outcomes. This mutation increases thrombotic burden, intracranial hemorrhages, and mortality in both mouse models and human patients with CVST.
Area Of Science
- Neuroscience
- Hematology
- Genetics
Background
- Cerebral venous sinus thrombosis (CVST) is a rare stroke type with potential for severe outcomes.
- The JAK2V617F mutation, common in myeloproliferative neoplasms, is linked to poorer CVST prognosis.
Purpose Of The Study
- To investigate if hematopoietic JAK2V617F expression influences CVST pathophysiology and patient outcomes.
- To compare clinical, biological, and imaging results in mice and humans with and without the JAK2V617F mutation.
Main Methods
- Utilized an in vivo mouse model of CVST with hematopoietic-restricted Jak2V617F expression.
- Analyzed clinical, biological, and imaging data in JAK2V617F-positive and negative human CVST cohorts.
- Assessed platelet-neutrophil adhesion, intracranial hemorrhages, mortality, neutrophil activation markers, and blood-brain barrier integrity.
Main Results
- Mice with hematopoietic Jak2V617F expression showed increased platelet-neutrophil adhesion in cerebral veins.
- Jak2V617F mice exhibited higher rates of intracranial hemorrhages and mortality.
- Elevated circulating platelet-neutrophil aggregates, CD11b expression, and myeloperoxydase levels were observed in Jak2V617F mice.
- Human JAK2V617F-positive CVST patients had greater thrombotic burden and a higher systemic immune-inflammation index.
Conclusions
- Hematopoietic JAK2V617F expression in CVST leads to increased thrombotic burden, intracranial hemorrhages, and mortality.
- An exacerbated thromboinflammatory response, driven by JAK2V617F, contributes to CVST severity and hemorrhagic complications in both mice and humans.
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