title: Proof-of-principle investigation of an algorithmic model of adenosine-mediated angiogenesis.
abstract: BACKGROUND
  We investigated an algorithmic approach to modelling angiogenesis controlled by vascular endothelial growth factor (VEGF), the anti-angiogenic soluble VEGF receptor 1 (sVEGFR-1) and adenosine (Ado). We explored its feasibility to test angiogenesis-relevant hypotheses. We illustrated its potential to investigate the role of Ado as an angiogenesis modulator by enhancing VEGF activity and antagonizing sVEGFR-1.
  
  
  RESULTS
  We implemented an algorithmic model of angiogenesis consisting of the dynamic interaction of endothelial cells, VEGF, sVEGFR-1 and Ado entities. The model is based on a logic rule-based methodology in which the local behaviour of the cells and molecules is encoded using if-then rules. The model shows how Ado may enhance angiogenesis through activating and inhibiting effects on VEGF and sVEGFR-1 respectively. Despite the relative simplicity of the model, it recapitulated basic features observed in in vitro models. However, observed disagreements between our models and in vitro data suggest possible knowledge gaps and may guide future experimental directions.
  
  
  CONCLUSIONS
  The proposed model can support the exploration of hypotheses about the role of different molecular entities and experimental conditions in angiogenesis. Future expansions can also be applied to assist research planning in this and other biomedical domains.
authors.affiliation: Laboratory of Cardiovascular Research, Centre de Recherche Public-Santé (CRP-Santé), L-1150 Luxembourg, Luxembourg. Francisco.Azuaje@crp-sante.lu
authors.forename: Francisco
authors.initials: F
authors.lastname: Azuaje
authors.forename: Frédérique
authors.initials: F
authors.lastname: Léonard
authors.forename: Magali
authors.initials: M
authors.lastname: Rolland-Turner
authors.forename: Yvan
authors.initials: Y
authors.lastname: Devaux
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Wagner
mesh_terms: D000241:Adenosine / Q000494:pharmacology*; D000465:Algorithms; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D015203:Reproducibility of Results; D012995:Solubility / Q000187:drug effects; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
chemical_list: D040281:Vascular Endothelial Growth Factor Receptor-1; D000241:Adenosine