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Vascular endothelial cell expression of JAK2V617F is sufficient to promote a pro-thrombotic state due to increased P-selectin expression

dc.rights.licenseopenen_US
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGUY, Alexandre
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorGOURDOU-LATYSZENOK, Virginie
dc.contributor.authorLE LAY, Nicolas
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorPEGHAIRE, Claire
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorKILANI, Badr
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDIAS, Juliana Vieira
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorDUPLAA-COUFFINHAL, Cécile
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorRENAULT, Marie-Ange
dc.contributor.authorDENIS, Cécile
dc.contributor.authorVILLEVAL, Jean Luc
dc.contributor.authorBOULAFTALI, Yacine
dc.contributor.authorJANDROT-PERRUS, Martine
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorCOUFFINHAL, Thierry
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloe
dc.date.accessioned2020-11-09T10:10:00Z
dc.date.available2020-11-09T10:10:00Z
dc.date.issued2019-01
dc.identifier.issn1592-8721en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/12140
dc.description.abstractEnThrombosis is the main cause of morbidity and mortality in patients with JAK2V617F myeloproliferative neoplasms. Recent studies have reported the presence of JAK2V617F in endothelial cells of some patients with myeloproliferative neoplasms. We investigated the role of endothelial cells that express JAK2V617F in thrombus formation using an in vitro model of human endothelial cells overexpressing JAK2V617F and an in vivo model of mice with endothelial-specific JAK2V617F expression. Interestingly, these mice displayed a higher propensity for thrombus. When deciphering the mechanisms by which JAK2V617F-expressing endothelial cells promote thrombosis, we observed that they have a pro-adhesive phenotype associated with increased endothelial P-selectin exposure, secondary to degranulation of Weibel-Palade bodies. We demonstrated that P-selectin blockade was sufficient to reduce the increased propensity of thrombosis. Moreover, treatment with hydroxyurea also reduced thrombosis and decreased the pathological interaction between leukocytes and JAK2V617F-expressing endothelial cells through direct reduction of endothelial P-selectin expression. Taken together, our data provide evidence that JAK2V617F-expressing endothelial cells promote thrombosis through induction of endothelial P-selectin expression, which can be reversed by hydroxyurea. Our findings increase our understanding of thrombosis in patients with myeloproliferative neoplasms, at least those with JAK2V617F-positive endothelial cells, and highlight a new role for hydroxyurea. This novel finding provides the proof of concept that an acquired genetic mutation can affect the pro-thrombotic nature of endothelial cells, suggesting that other mutations in endothelial cells could be causal in thrombotic disorders of unknown cause, which account for 50% of recurrent venous thromboses.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial 3.0 United States
dc.rights.urihttp://creativecommons.org/licenses/by-nc/3.0/us/
dc.subjectArticle RECHERCHE
dc.title.enVascular endothelial cell expression of JAK2V617F is sufficient to promote a pro-thrombotic state due to increased P-selectin expression
dc.typeArticle de revueen_US
dc.identifier.doi10.3324/haematol.2018.195321en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
dc.identifier.pubmed30171023en_US
bordeaux.journalHaematologicaen_US
bordeaux.page70–81en_US
bordeaux.volume104en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-02995532
hal.version1
hal.date.transferred2020-11-09T10:10:05Z
hal.exporttrue
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