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Erythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm

dc.contributor.authorPOISSON, Johanne
dc.contributor.authorTANGUY, Marion
dc.contributor.authorDAVY, Hortense
dc.contributor.authorCAMARA, Fatoumata
dc.contributor.authorEL MDAWAR, Marie-Belle
dc.contributor.authorKHELOUFI, Marouane
dc.contributor.authorDAGHER, Tracy
dc.contributor.authorDEVUE, Cécile
dc.contributor.authorLASSELIN, Juliette
dc.contributor.authorPLESSIER, Aurelie
dc.contributor.authorMERCHANT, Salma
dc.contributor.authorBLANC-BRUDE, Olivier
dc.contributor.authorSOUYRI, Michele
dc.contributor.authorMOUGENOT, Nathalie
dc.contributor.authorDINGLI, Florent
dc.contributor.authorLOEW, Damarys
dc.contributor.authorHATEM, Stephane N.
hal.structure.identifierBiologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases
dc.contributor.authorJAMES, Chloe
dc.contributor.authorVILLEVAL, Jean-Luc
dc.contributor.authorBOULANGER, Chantal M.
dc.contributor.authorRAUTOU, Pierre-Emmanuel
dc.date.accessioned2020-10-19T14:25:05Z
dc.date.available2020-10-19T14:25:05Z
dc.date.issued2020-04-19
dc.identifier.issn1558-8238en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/11434
dc.description.abstractEnArterial cardiovascular events are the leading cause of death in patients with JAK2V617F myeloproliferative neoplasms (MPN). However, their mechanisms are poorly understood. The high prevalence of myocardial infarction without significant coronary stenosis or atherosclerosis in patients with MPN suggests that vascular function is altered. Consequences of JAK2V617F mutation on vascular reactivity are unknown. We observe here increased responses to vasoconstrictors in arteries from Jak2V617F mice, resulting from disturbed endothelial nitric oxide pathway and increased endothelial oxidative stress. This response was reproduced in wild-type mice by circulating microvesicles isolated from patients carrying JAK2V617F and by erythrocyte-derived microvesicles from transgenic mice. Microvesicles of other cellular origins had no effect. This effect was observed ex vivo on isolated aortas, but also in vivo on femoral arteries. Proteomic analysis of microvesicles derived from JAK2V617F erythrocytes identified increased expression of myeloperoxidase as the likely mechanism accounting for microvesicles effect. Myeloperoxidase inhibition in microvesicles derived from JAK2V617F erythrocytes supressed their effect on oxidative stress. Antioxidants, such as simvastatin and N-acetyl-cysteine, improved arterial dysfunction in Jak2V617F mice. In conclusion, JAK2V617F MPN are characterized by exacerbated vasoconstrictor responses resulting from increased endothelial oxidative stress caused by circulating erythrocyte-derived microvesicles. Simvastatin appears as promising therapeutic strategy in this setting.
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States
dc.subject.enRecherche
dc.title.enErythrocyte-derived microvesicles induce arterial spasms in JAK2V617F myeloproliferative neoplasm
dc.title.alternativeJ Clin Investen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1172/JCI124566en_US
dc.subject.halSciences du Vivant [q-bio]/Médecine humaine et pathologieen_US
bordeaux.journalJournal of Clinical Investigationen_US
bordeaux.page2630–2643en_US
bordeaux.volume130en_US
bordeaux.hal.laboratoriesBiologie des maladies cardiovasculaires - U1034en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.exportfalse
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