Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea

Haematologica
Flavia C M LopesNicola Conran

Abstract

As hypoxia-induced inflammatory angiogenesis may contribute to the manifestations of sickle cell disease, 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 patients with steady-state sickle cell anemia contained 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 increasing endothelial cell proliferation, migration and capillary-like structure formation. In vivo neovascularization of Matrigel plugs was significantly greater in sickle cell disease mice than in non-sickle cell disease mice, consistent with an up-regulation 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 had a pro-angiogenic profi...Continue Reading

Citations

Apr 8, 2016·Current Opinion in Hematology·Gregory J Kato
Nov 23, 2016·Nitric Oxide : Biology and Chemistry·Iakovos ArmenisIoannis Rombos
Jan 22, 2019·Stroke; a Journal of Cerebral Circulation·Kristin P GuilliamsMichael M Dowling
Sep 12, 2019·Blood Advances·Atinuke M Dosunmu-OgunbiAdam C Straub
Jun 24, 2017·Experimental Hematology & Oncology·Silvia R BrandalisePedro O de Campos-Lima
Apr 5, 2019·Blood Advances·Kalpna GuptaRobert P Hebbel
Aug 19, 2017·Expert Review of Hematology·Natalie R Shilo, Claudia R Morris
Apr 5, 2018·Clinical Hemorheology and Microcirculation·Nicola Conran, John D Belcher
Mar 25, 2019·The American Journal of Pathology·Junaid Ansari, Felicity N E Gavins

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