Beta-adrenergic adaptation in idiopathic dilated cardiomyopathy: differences between children and adults

This editorial refers to ‘Beta-adrenergic adaptation in paediatric idiopathic dilated cardiomyopathy’, by S.D. Miyamoto et al. , doi:10.1093/eurheartj/ehs229 The study of Miyamoto et al .1 found differences in beta-adrenergic adaptation to heart failure (HF) in explanted heart tissue between children and adults with symptomatic dilated cardiomyopathy (DCM). Differences included: (i) down-regulation of beta-1- and beta-2-adrenergic receptors in children but maintained beta-2-adrenergic receptor expression in adults; and (ii), in children, uncoupling of the beta-1-adrenergic receptors and stimulatory G-proteins, among others.1An important family of cell surface protein receptors, the G-protein-coupled receptors (GPCRs), enable cells to sense and respond to outside signals. For children with cardiomyopathy and heart failure, we need a better understanding of the structure–function relationships and the detailed regulation of GCPRs, as well as the drugs that stimulate or inhibit these relationships. Understanding beta-adrenergic adaptation in children with HF should indicate how cardiomyocytes interact with their extracellular environment and adapt to new situations, such as when epinephrine acts on cells to increase blood pressure and heart rate.Miyamoto and colleagues observed that the GCPR signalling system has become the target of prescription drugs, including beta-blockers, to relieve HF.1 In fact, about half of all medications act on these receptors, so learning about them is key to developing better drugs.The GPCR initiates a cascade of signals into the cell, prompting it to respond appropriately, as well as a secondary cascade in which a feedback signal leads to desensitization. A molecule called beta-arrestin binds to the GPCR and reduces or temporarily stops GPCR's sensitivity.Beta-arrestin, in addition to receptor desensitization, is involved in receptor endocytosis and activating extracellular signal-regulated kinase (ERK) and other …