TY - JOUR
T1 - Proof-of-principle investigation of an algorithmic model of adenosine-mediated angiogenesis
AU - Azuaje, Francisco
AU - Léonard, Frédérique
AU - Rolland-Turner, Magali
AU - Devaux, Yvan
AU - Wagner, Daniel R.
N1 - Funding Information:
We thank Christelle Nicolas for technical assistance. This study was in part supported by grants from the Ministry of Culture, Higher Education and Research of Luxembourg. FL is recipient of a fellowship from the National Fund for Research of Luxembourg.
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79953749308&partnerID=8YFLogxK
U2 - 10.1186/1742-4682-8-7
DO - 10.1186/1742-4682-8-7
M3 - Article
C2 - 21477269
AN - SCOPUS:79953749308
SN - 1742-4682
VL - 8
JO - Theoretical Biology and Medical Modelling
JF - Theoretical Biology and Medical Modelling
IS - 1
M1 - 7
ER -