Angiogenic characteristics of blood outgrowth endothelial cells from patients with von Willebrand disease

Summary Background Endothelial von Willebrand factor (VWF) inhibits angiogenesis. Accordingly, blood outgrowth endothelial cells (BOECs) isolated from von Willebrand disease (VWD) patients showed enhanced in vitro angiogenesis when compared with healthy control BOECs. Characterization of the angioge...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis 2015-10, Vol.13 (10), p.1854-1866
Main Authors: Groeneveld, D. J., Bekkum, T., Dirven, R. J., Wang, J.‐W., Voorberg, J., Reitsma, P. H., Eikenboom, J.
Format: Article
Language:English
Subjects:
Angiogenesis
Blood
Case-Control Studies
Cell adhesion & migration
cell migration
Cell Movement
Cell Separation
Cells, Cultured
endothelial cells
Endothelial Cells - metabolism
Genetic Predisposition to Disease
Heterozygote
Humans
Mutation
Neovascularization, Physiologic - genetics
Patients
Phenotype
Signal Transduction
von Willebrand disease
von Willebrand disease, type 3
von Willebrand Diseases - blood
von Willebrand Diseases - genetics
von Willebrand Diseases - physiopathology
von Willebrand factor
von Willebrand Factor - genetics
von Willebrand Factor - metabolism
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Summary:Summary Background Endothelial von Willebrand factor (VWF) inhibits angiogenesis. Accordingly, blood outgrowth endothelial cells (BOECs) isolated from von Willebrand disease (VWD) patients showed enhanced in vitro angiogenesis when compared with healthy control BOECs. Characterization of the angiogenic response of VWD BOECs is limited and differences between the different types of VWD have not been investigated in detail. Objectives The aim of this study was to further explore the potential pathogenic effect of VWF mutations on angiogenesis. Methods BOECs were isolated from four healthy individuals, 10 patients with VWD and one heterozygous carrier of a type 2N mutation. Cell migration and tube formation were measured. Results Migration velocity and total tube formation were similar between VWD patients and controls in general. BOECs from the type 3 VWD patient and one type 2B patient showed increased migratory velocity and tube formation compared with BOECs from other patients and healthy controls. Directional migration was impaired in eight out of 10 VWD BOECs and the ability to form tubes was limited to early passage numbers, but not for BOECs from healthy controls. Conclusion BOECs can be a useful tool for ex vivo assessment of endothelial cell function in patients with different types of VWD, but possible limitations, such as early loss of angiogenic capacity, should be recognized. BOECs from most VWD patients consistently showed impairment in the directionality of migration. This is the first report on angiogenic properties of a type 3 VWD BOEC, which showed increased in vitro angiogenesis.
ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.13112