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A mathematical model of cGMP signaling and VASP phosphorylation in platelets was developed and validated using experimental data, allowing for the quantitative prediction of drug effects.
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A validated mathematical model of cGMP signaling and VASP phosphorylation in platelets allows for quantitative prediction of drug effects on inhibitory cyclic nucleotide pathways.
Background The cyclic nucleotides cAMP and cGMP inhibit platelet activation. Results We extended an older model and systematically integrated drugs as external stimuli. Data driven modeling allowed us to design models that provide a quantitative output for quantitative input information. This relies on condensed information about involved regulation and modeling of pharmacological interventions by systematic optimization methods. By multi-experiment fitting, we validated our model optimizing the parameters of the model. In addition, we show how the output of the developed cGMP model can be used as input for a modular model of VASP phosphorylation and for the activity of cAMP and cGMP pathways in platelets. Conclusions We present a model for cGMP signaling and VASP phosphorylation, that allows to estimate drug action on any of the inhibitory cyclic nucleotide pathways (cGMP, cAMP) and has been validated by experimental data.
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Breitenbach et al. (2021) studied Platelet activation and cGMP signaling. sGC stimulators (SNP, BAY 41-2272, Riociguat) vs. Control / ODQ (sGC inhibitor) was evaluated on cGMP levels and VASP phosphorylation. A mathematical model of cGMP signaling and VASP phosphorylation in platelets was developed and validated using experimental data, allowing for the quantitative prediction of drug effects.
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