Computational model of VEGF, thrombin and histamine signalling network

Endothelial permeability is involved in a number of diseases. Three key mediators, thrombin, histamine, and VEGF induce endothelial permeability partly via activating myosin light chain (MLC) via specific pathways. Quantitative analysis of the relevant signaling events are important for facilitating the understanding of the molecular mechanism and signaling dynamics leading to endothelial permeability. Ordinary differential equation (ODE) based mathematical models have been developed and used for simulating MLC activation by the thrombin-mediated pathway and by Ca²⁺ and MLCK. Additional mathematical models need to be developed to facilitate more comprehensive analysis of the signaling events and regulations in endothelial permeability. By extending the published simulation models, we reproduced simulation model of the thrombin-mediated pathway and developed new simulation models of the histamine-mediated and VEGF-mediated pathways, which were validated by available experimental and simulation results.