Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/201476
Type: Artigo de periódico
Title: In Vitro And In Vivo Anti-angiogenic Effects Of Hydroxyurea.
Author: Lopes, Flávia Cristine Mascia
Ferreira, Regiane
Albuquerque, Dulcinéia Martins
Silveira, Angélica A Antoniellis
Costa, Raquel
Soares, Raquel
Costa, Fernando Ferreira
Conran, Nicola
Abstract: Hydroxyurea (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.
Subject: Angiogenesis
Capillary Formation
Endothelial Cells
Hydroxyurea
Hypoxia
Inflammation
Leg Ulcer
Myeloproliferative Diseases
Sickle Cell Disease
Mirna
Rights: fechado
Identifier DOI: 10.1016/j.mvr.2014.05.009
Address: http://www.ncbi.nlm.nih.gov/pubmed/24925859
Date Issue: 2014
Appears in Collections:Unicamp - Artigos e Outros Documentos

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