Isoproterenol decreased intracellular iron levels and altered cardiac iron metabolism comparably to deferoxamine in H9c2 cells, suggesting beta-adrenergic stimulation contributes to iron deficiency.
Beta-adrenergic stimulation induces intracellular iron depletion and alters iron metabolism in cardiac cells similarly to iron chelation, suggesting a mechanism for the development of iron deficiency in heart failure.
Iron deficiency (ID) is frequent in patients with heart failure (HF) and is correlated with adverse outcomes, yet its involvement in HF pathophysiology is not fully understood. Hyperactivity of the sympathetic nervous system (SNS) is the central feature of HF. We aimed to compare the effects of isoproterenol (ISO), a β-adrenergic agonist (SNS stimulation), with those of the iron chelator deferoxamine (DEF), to evaluate how β-adrenergic stimulation influences cardiac iron. In this study, H9c2 cardiac cells were challenged with ISO, DEF or both and several parameters related to iron metabolism were analyzed. In all cases, the cells decreased their intracellular iron levels. ISO induced alterations in key cardiac iron metabolism molecules that were, in most cases, comparable to those elicited by DEF, emphasizing the direct impact of β-adrenergic stimuli on iron metabolism and mitochondrial dysfunction. Nevertheless, unlike DEF, ISO triggered a shift in mitochondrial energy metabolism. These findings suggest that β-adrenergic stimulation, as a major component of neurohormonal activation, may contribute to the development of ID in cardiac cells, highlighting the importance of iron homeostasis and the need to further investigate iron dysregulation in this context.
Francesch-Manzano et al. (Tue,) conducted a other in Heart failure. Isoproterenol (ISO) vs. Deferoxamine (DEF) was evaluated on Intracellular iron levels and iron metabolism molecules. Isoproterenol decreased intracellular iron levels and altered cardiac iron metabolism comparably to deferoxamine in H9c2 cells, suggesting beta-adrenergic stimulation contributes to iron deficiency.