Global Sensitivity Analysis of a Novel Signaling Network for Heart Growth With Local IGF1 Production

Abstract

Signaling networks can be used to describe the dynamic interplay of hormonal and mechanical factors that regulate heart growth. However, a qualitative analysis of signaling networks is often difficult due to their complexity and nonlinear behavior. In this work, a global sensitivity analysis of signaling networks is conducted to determine the most influential factors for heart growth over a range of model inputs. Furthermore, the local production of the hormone insulin-like growth factor 1 (IGF1) in response to high mechanical stretches as recently described by Zaman et al.(Immunity, 54, 2057) and Wong et al.(Immunity, 54, 2072) is incorporated. The computational results show that this increases the influence of mechanical stretch on heart growth significantly. Further key influential factors are the hormones norepinephrine (NE), angiotensin II (AngII), and globally produced IGF1 (g-IGF1). Our sensitivity analysis indicates that the novel consideration of local IGF1 (l-IGF1) production has to be considered in signaling networks for heart growth.