Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
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Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells

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Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells

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dc.contributor.author Pérez-Cremades, Daniel
dc.contributor.author Bueno-Betí, Carlos
dc.contributor.author García-Giménez, José Luis
dc.contributor.author Ibañez-Cabellos, José Santiago
dc.contributor.author Hermenegildo, Carlos
dc.contributor.author Pallardó, Federico V.
dc.contributor.author Novella, Susana
dc.date.accessioned 2020-09-30T17:21:34Z
dc.date.available 2020-09-30T17:21:34Z
dc.date.issued 2017
dc.identifier.uri https://hdl.handle.net/10550/75709
dc.description.abstract Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone-mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose-dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase-2 (COX-2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX-1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX-2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial-dependent mediators through an up-regulation in COX-2-PGIS-PGI2 pathway which involves a COX-2-dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone-mediated pathologies.
dc.language.iso eng
dc.relation.ispartof Journal Of Cellular And Molecular Medicine, 2017, vol. 21, num. 8, p. 1584-1592
dc.rights.uri info:eu-repo/semantics/openAccess
dc.source Pérez-Cremades, Daniel Bueno-Betí, Carlos García-Giménez, José Luis Ibañez-Cabellos, José Santiago Hermenegildo, Carlos Pallardó, Federico V. Novella, Susana 2017 Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells Journal Of Cellular And Molecular Medicine 21 8 1584 1592
dc.subject Òxid nítric
dc.subject Proteïnes
dc.subject Genètica humana
dc.title Extracellular histones disarrange vasoactive mediators reléase through COX-NOS interaction in human endothelial cells
dc.type info:eu-repo/semantics/article
dc.date.updated 2020-09-30T17:21:34Z
dc.identifier.doi https://doi.org/10.1111/jcmm.13088
dc.identifier.idgrec 115008

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