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Thromboinflammation in ischemic cerebrovascular patients with the JAK2V617F mutation

Marie Hvelplund Kristiansen1, Morten Kranker Larsen2, Laura Massarenti3

  • 1Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Neurology, Zealand University Hospital, Roskilde, Denmark.

Thrombosis Research
|December 9, 2024
PubMed
Abstract

Insights

The JAK2V617F mutation in stroke patients is linked to increased inflammation and endothelial dysfunction, particularly with higher mutation burdens. This highlights inflammation

Area of Science:

  • Hematology
  • Cardiovascular Science
  • Molecular Biology

Background:

  • The JAK2V617F mutation drives Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and is linked to cardiovascular issues.
  • Thrombosis in MPNs involves JAK2V617F-associated platelet activation and endothelial dysfunction, potentially influenced by chronic inflammation.
  • The impact of the JAK2V617F mutation on thromboinflammatory markers in non-MPN patients is not well understood.

Purpose of the Study:

  • To investigate the association between the JAK2V617F mutation and thromboinflammatory markers in patients with ischemic cerebrovascular disease.
  • To determine if the JAK2V617F mutation influences markers of endothelial dysfunction and inflammation in stroke patients.

Main Methods:

  • A case-control study involving 63 ischemic cerebrovascular patients with the JAK2V617F mutation and 63 matched controls without the mutation.
  • Serum samples were analyzed for 12 thromboinflammatory markers at the acute phase and at a three-month follow-up.
  • Subgroup analysis and regression analysis were performed to assess the impact of JAK2V617F allele burden.

Main Results:

  • No overall significant difference in thromboinflammatory markers between cases and controls.
  • Patients with JAK2V617F allele burden ≥1% showed higher baseline Vascular Cell Adhesion Molecule-1 (VCAM-1).
  • Elevated Interleukin-10 (IL-10) and Tumor Necrosis Factor α (TNF-α) were observed at follow-up in patients with higher allele burden, with significant associations found via regression analysis.

Conclusions:

  • The JAK2V617F mutation is associated with elevated markers of endothelial dysfunction and chronic inflammation in ischemic cerebrovascular patients.
  • Higher JAK2V617F allele burden correlates with increased VCAM-1, IL-10, and TNF-α.
  • Inflammation plays a significant role in thrombosis driven by the JAK2V617F mutation.
Keywords:
Clonal hematopoiesisIschemic strokeJanus kinase 2Myeloproliferative disordersThromboinflammationThrombosis

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