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Contributions of mechanical loading and hormonal changes to eccentric hypertrophy during volume overload: A Bayesian analysis using logic-based network models

Fig 6

Validation of model predictions of growth during infusion of hypertrophic agonists with and without receptor blockers.

a) Boxplot shows the mean, 50% confidence interval, and 90% confidence interval for predicted normalized growth in 1000 MC simulations of ISO infusion with the calibrated network. Twelve of 15 experimental means (plotted as individual points with error bars) from [86–97] fell within the CI90. b) Model-predicted CI90 for growth during AngII infusion encompassed most published values at the earliest time point and all reported experimental means at later time points [98–111]. c) Simulations of four NE infusion experiments in dogs with different doses, fold increases in plasma concentrations (Conc.), and termination times showed reasonable agreement with the limited available data [112–115]. d) Simulations of agonist infusion plus receptor blockers replicated reported significant effects of β blockers (βB) on ISO-induced hypertrophy infusion [88,95,116,117], and smaller effects that were significant in some but not all studies for ARB administration during ISO infusion [86,96,97,117,118] or ERA administration during AngII infusion [111,119,120]. By contrast, the model prediction of nearly equal likelihood that ERA increases or decreases NE-induced growth appears to contradict a significant reported decrease in the only available experimental study [121]. Red coloring of boxplots indicates increases in >75% of simulations, blue indicates decreases in more than 75%, and gray indicates mixed results. Points with error bars indicate experimental mean±SD for studies reporting statistically significant effects (filled markers) or non-significant effects (open markers), from studies in dogs (circles) or rats (triangles).

doi: https://doi.org/10.1371/journal.pcbi.1012390.g006