In contrast to Fpn fl/fl Myh6.Cre+ mice, patients with ferroportin
disease, an inherited disorder of iron metabolism caused
by dominant loss of FPN function, have not been reported to
have cardiac complications (27, 28). However, although Fpn fl/fl
Myh6.Cre+ mice retain intact FPN function in the duodenum,
liver, and reticuloendothelial system, patients with ferroportin
disease do not, leading to iron accumulation in the spleen and
liver, reduced circulating Tf and NTBI, and marginal anemia
(28). Given the known role of NTBI in cardiac iron overload, it
is plausible that decreased NTBI entry into cardiomyocytes in
these patients offsets the iron-loading effects of loss of cardiac
FPN. This hypothesis is supported by our finding that dietary iron restriction protects Fpn fl/fl Myh6.Cre+ mice from developing
cardiac dysfunction