Fig. 3
Brain–heart sympathetic pathway at the molecular level. The “fight or flight” response of catecholaminergic storm, followed by hypothalamic–pituitary–adrenal axis and autonomic activation, is represented at the molecular level. Synaptic connection through neurons and myocytes is represented. Noradrenaline activates β1 receptors, which in turn activates cyclic adenosine monophosphate–protein kinase A (cAMP–PKA) signaling, with consequent release of Ca2+ from the sarcoplasmic reticulum for cell contraction. At the same time, noradrenaline activates β2 receptors, which, acting through the protein kinase B (Akt)-FOXO pathway, decrease protein degradation by ubiquitin, thus regulating cardiomyocyte proteostatic equilibrium and cardiac mass maintenance with muscle ring finger-1 (MuRF-1), which is upregulated in the deficient heart. FOXO, forkhead box O; Akt, protein kinase B; PKA, protein kinase A; cAMP, cyclic adenosine monophosphate, ATP, adenosine triphosphate; MuRF-1, muscle ring finger-1. Modified from "Martini FH. Fundamentals of Anatomy and Physiology. 8th ed. 2006. Chapter 20"