Key Endothelial Cell Angiogenic Mechanisms Are Stimulated By The Circulating Milieu In Sickle Cell Disease And Attenuated By Hydroxyurea.

dc.creatorLopes, Flavia C M
dc.creatorTraina, Fabiola
dc.creatorAlmeida, Camila B
dc.creatorLeonardo, Flavia C
dc.creatorFranco-Penteado, Carla F
dc.creatorGarrido, Vanessa T
dc.creatorColella, Marina P
dc.creatorSoares, Raquel
dc.creatorOlalla-Saad, Sara T
dc.creatorCosta, Fernando F
dc.creatorConran, Nicola
dc.date2015-Mar
dc.date2015-11-27T13:46:25Z
dc.date2015-11-27T13:46:25Z
dc.date.accessioned2018-03-29T01:23:53Z
dc.date.available2018-03-29T01:23:53Z
dc.identifierHaematologica. , 2015-Mar.
dc.identifier1592-8721
dc.identifier10.3324/haematol.2014.119727
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/25769545
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/202217
dc.identifier25769545
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1302450
dc.descriptionAs hypoxia-induced inflammatory angiogenesis may contribute to sickle cell disease manifestations, we compared the angiogenic molecular profiles of plasma from sickle cell disease individuals and correlated these with in vitro endothelial cell-mediated angiogenesis-stimulating activity and in vivo neovascularization. Bioplex demonstrated that plasma from steady-state sickle cell anemia patients presented elevated concentrations of pro-angiogenic factors (Angiopoietin-1, basic fibroblast growth factor, vascular endothelial growth factor, vascular endothelial growth factor-D and placental growth factor) and displayed potent pro-angiogenic activity, significantly augmenting endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice, compared with non-sickle cell disease mice, consistent with an upregulation of angiogenesis in the disease. In plasma from patients with hemoglobin SC disease without proliferative retinopathy, anti-angiogenic endostatin and thrombospondin-2 were significantly elevated. In contrast, plasma from hemoglobin SC individuals with proliferative retinopathy displayed a pro-angiogenic profile and had more significant effects on endothelial cell proliferation and capillary formation than plasma of patients without retinopathy. Hydroxyurea therapy was associated with significant reductions in plasma angiogenic factor profile, in association with an inhibition of endothelial cell-mediated angiogenic mechanisms and neovascularization. Thus, sickle cell anemia and retinopathic hemoglobin SC individuals present a highly angiogenic circulating milieu, capable of stimulating key endothelial cell-mediated angiogenic mechanisms. Combination anti-angiogenic therapy for preventing progression of unregulated neovascularization and associated manifestations in sickle cell disease, such as pulmonary hypertension, may be indicated; furthermore, the benefits and drawbacks of the potent anti-angiogenic effects of hydroxyurea should be clarified.
dc.description
dc.description
dc.languageeng
dc.relationHaematologica
dc.relationHaematologica
dc.rightsaberto
dc.rightsCopyright © 2015, Ferrata Storti Foundation.
dc.sourcePubMed
dc.subjectAngiogenesis
dc.subjectHemoglobinopathies
dc.subjectHydroxyurea
dc.subjectVascular Wall Biology And Platelet Adhesion
dc.titleKey Endothelial Cell Angiogenic Mechanisms Are Stimulated By The Circulating Milieu In Sickle Cell Disease And Attenuated By Hydroxyurea.
dc.typeArtículos de revistas


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