title: Differential effects of fondaparinux and bemiparin on angiogenic and vasculogenesis-like processes.
abstract: BACKGROUND
  Conventional therapy for venous thromboembolism or acute coronary syndrome involves the administration of glycoanticoagulants (heparins) or oligosaccharides (fondaparinux). We evaluated the effects of such drugs on angiogenesis and vasculogenesis-like models.
  
  
  METHODS
  Human umbilical vein endothelial cells or human endothelial progenitor cells were treated with bemiparin, fondaparinux or unfractionated heparin, at concentrations reflecting the doses used in clinical practice. After 24h, cell viability, proliferation, tubule formation and angiogenic molecular mechanisms, such as activation of the serine/threonine kinase AKT, were assessed. In vivo angiogenesis was studied using a Matrigel sponge assay in mice.
  
  
  RESULTS
  Bemiparin gave a significant decrease of in vitro angiogenesis as shown by the reduction of endothelial cell tubule network, while both fondaparinux and unfractionated heparin did not show any significant effect. In assays of Matrigel sponge invasion in mice, unfractionated heparin was able to stimulate angiogenesis and, conversely, bemiparin inhibited angiogenesis. Furthermore, both bemiparin and fondaparinux caused a significant reduction in an in vitro vasculogenesis-like model, as demonstrated by the decrease of tubule network after co-seeding of endothelial progenitor cells and human umbilical vein endothelial cells. In addition, unfractionated heparin but not bemiparin was able to increase AKT phosphorylation.
  
  
  CONCLUSIONS
  In in vitro experiments, bemiparin was the only drug to show an anti-angiogenic and vasculogenic-like effect, unfractionated heparin showed only a trend to increase in angiogenesis assay and fondaparinux affected only the vasculogenesis-like model. Notably, the in vivo experiments corroborated these data. Such results are important for the choice of a patient-tailored therapy.
authors.affiliation: Department of Psychiatry, Neurobiology, Pharmacology and Biotechnology, University of Pisa, Pisa, Italy. dapozzo@farm.unipi.it
authors.forename: Eleonora
authors.initials: E
authors.lastname: Da Pozzo
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Barsotti
authors.forename: Sara
authors.initials: S
authors.lastname: Bendinelli
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.forename: Alberto
authors.initials: A
authors.lastname: Balbarini
authors.forename: Claudia
authors.initials: C
authors.lastname: Martini
authors.forename: Rossella
authors.initials: R
authors.lastname: Di Stefano
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D000077425:Fondaparinux; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight; D011134:Polysaccharides; D000077425:Fondaparinux; C411345:bemiparin