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Exacerbation of thrombo-inflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis.

dc.rights.licenseopenen_US
dc.contributor.authorBOURRIENNE, Marie-Charlotte
dc.contributor.authorLE CAM DUCHEZ, Véronique
dc.contributor.authorFAILLE, Dorothée
dc.contributor.authorFARKH, Carine
dc.contributor.authorSOLO NOMENJANAHARY, Mialitiana
dc.contributor.authorGAY, Juliette
dc.contributor.authorLOYAU, Stéphane
dc.contributor.authorJOURNÉ, Clément
dc.contributor.authorDUPONT, Sébastien
dc.contributor.authorOLLIVIER, Véronique
dc.contributor.authorVILLEVAL, Jean-Luc J-L
dc.contributor.authorPLO, Isabelle
dc.contributor.authorEDMOND, Valérie
dc.contributor.authorJANDROT-PERRUS, Martine
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorLABROUCHE-COLOMER, Sylvie
dc.contributor.authorCASSINAT, Bruno
dc.contributor.authorVERGER, Emmanuelle
dc.contributor.authorDESILLES, Jean-Philippe
dc.contributor.authorHO TIN NOÉ, Benoît Ho
dc.contributor.authorTRIQUENOT BAGAN, Aude
dc.contributor.authorMAZIGHI, Mikaël
dc.contributor.authorAJZENBERG, Nadine
dc.date.accessioned2024-03-25T16:04:57Z
dc.date.available2024-03-25T16:04:57Z
dc.date.issued2024-02-22
dc.identifier.issn2473-9537en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/188969
dc.description.abstractEnCerebral venous sinus thrombosis (CVST) is an uncommon venous thromboembolic event accounting for <1% of strokes resulting in brain parenchymal injuries. JAK2V617F mutation, the most frequent driving mutation of myeloproliferative neoplasms has been reported to be associated with worse clinical outcomes in patients with CVST. We investigated whether hematopoietic JAK2V617F expression predisposes to specific pathophysiological processes and/or worse prognosis after CVST. Using an in vivo mouse model of CVST, we analyzed clinical, biological and imaging outcomes in mice with hematopoietic-restricted Jak2V617F expression, compared to Jak2WT mice. In parallel, we studied a human cohort of JAK2V617F-positive or negative CVST. Early after CVST, mice with hematopoietic Jak2V617F expression had increased adhesion of platelets and neutrophils in cerebral veins located in the vicinity of CVST. On day 1, Jak2V617F mice had a worse outcome characterized by significantly more frequent and severe intracranial hemorrhages (ICH) and higher mortality rates. Peripheral neutrophil activation was enhanced, as indicated by higher circulating platelet-neutrophil aggregates, upregulated CD11b expression, and higher myeloperoxydase (MPO) plasma level. Concurrently, immunohistological and brain homogenates analysis showed higher neutrophil infiltration and increased blood-brain-barrier disruption. Similarly, JAK2V617F-positive CVST patients tended to present higher thrombotic burden and had significantly higher SII, a systemic thrombo-inflammatory marker, compared to JAK2V617F-negative patients. In mice with CVST, our study corroborates that Jak2V617F mutation leads to a specific pattern including increased thrombotic burden, ICH and mortality. The exacerbated thrombo-inflammatory response, observed both in mice and JAK2V617F-positive patients, could contribute to hemorrhagic complications.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.subject.enThrombosis and Hemostasis
dc.title.enExacerbation of thrombo-inflammation by JAK2V617F mutation worsens the prognosis of cerebral venous sinus thrombosis.
dc.title.alternativeBlood Adven_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1182/bloodadvances.2023011692en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed38386979en_US
bordeaux.journalBlood Advancesen_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires (BMC) - UMR 1034en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcepubmed
hal.identifierhal-04520587
hal.version1
hal.date.transferred2024-03-25T16:05:01Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
workflow.import.sourcepubmed
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&amp;rft_val_fmt=info:ofi/fmt:kev:mtx:journal&amp;rft.jtitle=Blood%20Advances&amp;rft.date=2024-02-22&amp;rft.eissn=2473-9537&amp;rft.issn=2473-9537&amp;rft.au=BOURRIENNE,%20Marie-Charlotte&amp;LE%20CAM%20DUCHEZ,%20V%C3%A9ronique&amp;FAILLE,%20Doroth%C3%A9e&amp;FARKH,%20Carine&amp;SOLO%20NOMENJANAHARY,%20Mialitiana&amp;rft.genre=article


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