Iron homeostasis. Heme-bound iron is transported from the gut lumen into the mucose cell through the heme carrier protein 1 (HCP1) and here Fe2 + is released by the activity of the heme-oxidase. Additionally, in the gut lumen Fe3 + is converted to Fe2 + by the ferri-reductase or through reduction by dietary ascorbate and then transported into the mucose cell through the divalent metal transporter 1 (DMT1). Fe2 + can be then converted again to Fe3 + and stored as ferritin, or exported to the bloodstream through ferroportin where it is converted to Fe3 + by hephaestin and binds to transferrin whose role is to transport iron where there is metabolic need. Macrophages contribute to iron homeostasis by taking up transferrin-bound iron by receptor-mediated endocytosis. In the macrophages iron can be stored as ferritin and released when needed through ferroportin. Inflammation leads to an increased release of hepcidin from the liver which downregulates ferroportin and therefore the transport of dietary intake from the inside of the mucosa cells in the small intestine to the bloodstream and also the release of recycled iron from macrophages in the spleen and the liver, potentially leading to iron deficiency. Created with BioRender.com Adapted from Nat Rev Cardiol 2015; 12: 659–669.⁵