In Vitro And In Vivo Anti-angiogenic Effects Of Hydroxyurea

dc.creatorLopes F.C.M.
dc.creatorFerreira R.
dc.creatorAlbuquerque D.M.
dc.creatorSilveira A.A.A.
dc.creatorCosta R.
dc.creatorSoares R.
dc.creatorCosta F.F.
dc.creatorConran N.
dc.date2014
dc.date2015-06-25T17:57:29Z
dc.date2015-11-26T14:52:06Z
dc.date2015-06-25T17:57:29Z
dc.date2015-11-26T14:52:06Z
dc.date.accessioned2018-03-28T22:04:05Z
dc.date.available2018-03-28T22:04:05Z
dc.identifier
dc.identifierMicrovascular Research. Academic Press Inc., v. 94, n. , p. 106 - 113, 2014.
dc.identifier262862
dc.identifier10.1016/j.mvr.2014.05.009
dc.identifierhttp://www.scopus.com/inward/record.url?eid=2-s2.0-84904611842&partnerID=40&md5=a7b6f604fbf9ad3d1ed84018704b1f18
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/87263
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/87263
dc.identifier2-s2.0-84904611842
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1254727
dc.descriptionHydroxyurea (HU), or hydroxycarbamide, is used for the treatment of some myeloproliferative and neoplastic diseases, and is currently the only drug approved by the FDA for use in sickle cell disease (SCD). Despite the relative success of HU therapy for SCD, a genetic disorder of the hemoglobin β chain that results in red-cell sickling, hemolysis, vascular inflammation and recurrent vasoocclusion, the exact mechanisms by which HU actuates remain unclear. We hypothesized that HU may modulate endothelial angiogenic processes, with important consequences for vascular inflammation. The effects of HU (50-200. μM; 17-24. h) on endothelial cell functions associated with key steps of angiogenesis were evaluated using human umbilical vein endothelial cell (HUVEC) cultures. Expression profiles of the HIF1A gene and the miRNAs 221 and 222, involved in endothelial function, were also determined in HUVECs following HU administration and the direct in vivo antiangiogenic effects of HU were assessed using a mouse Matrigel-plug neovascularization assay. Following incubation with HU, HUVECs exhibited high cell viability, but displayed a significant 75% inhibition in the rate of capillary-like-structure formation, and significant decreases in proliferative and invasive capacities. Furthermore, HU significantly decreased HIF1A expression, and induced the expression of miRNA 221, while downregulating miRNA 222. In vivo, HU reduced vascular endothelial growth factor (VEGF)-induced vascular development in Matrigel implants over 7. days. Findings indicate that HU is able to inhibit vessel assembly, a crucial angiogenic process, both in vitro and in vivo, and suggest that some of HU's therapeutic effects may occur through novel vascular mechanisms. © 2014 Elsevier Inc.
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dc.languageen
dc.publisherAcademic Press Inc.
dc.relationMicrovascular Research
dc.rightsfechado
dc.sourceScopus
dc.titleIn Vitro And In Vivo Anti-angiogenic Effects Of Hydroxyurea
dc.typeArtículos de revistas


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