Excess aldosterone and cortisol promote myocardial iron deficiency: A potential pathway to cardiac injury.

Mineralocorticoid receptor antagonists (MRAs) such as finerenone have shown clinical benefits in heart failure, yet their full mechanisms remain unclear. Recent evidence suggests a novel role of aldosterone in disrupting myocardial iron homeostasis. Aldosterone, via mineralocorticoid receptor (MR) activation, downregulates key iron transporters like transferrin receptor 1 (TfR1) through SGK1 signaling, contributing to myocardial iron deficiency (MID). Cortisol, which circulates at much higher levels than aldosterone and shares similar MR affinity, may similarly promote MID-especially in tissues like the heart where 11β-HSD2 activity is low. Iron deficiency in cardiomyocytes impairs mitochondrial function, reduces ATP synthesis, and promotes fibrosis and inflammation. MRAs may counteract these effects by restoring iron uptake and improving myocardial energetics. This emerging aldosterone-iron axis offers novel insight into the cardiac effects of MR activation and identifies iron homeostasis as a potential therapeutic target. Further research is warranted to explore MRA-mediated modulation of myocardial iron metabolism.