Table 2 Iron metabolism disturbances described in heart

Iron absorption

HO‐1

6 months of myricetin treatment (200 mg/kg/d) in DC mice

IκBα/NFκB inhibited and Nrf2/HO-1 enhanced

[104]

Cardiac hypertrophy, apoptosis, and interstitial fibrosis improved

Dcytb

In MDCK cells expressing an inducible duodenal cytochrome b-green fluorescent protein fusion construct

DMT1 and copper transporter 1 help Dcytb ingest iron and copper

[105]

Hephaestatin

The whole body and intestine-specific hephaestin knockout mice

Hephaestin is not necessary because both mouse strains survived

[106]

Duodenal enterocytes stored iron in knockout mice, reducing intestinal iron absorption

TFR1

Used wild-type and autophagy-deficient cells, BECN1^± and LC3B^−/−

During ferroptosis, ROS-induced autophagy controls ferritin degradation and TfR1 expression

[107]

DMT1

Acute myocardial infarction and cardiomyocyte hypoxia mouse models

DMT1 knockdown effectively decreased H/R-induced cardiac cell ferroptosis, while overexpression increased it

[108]

Iron storage

Ferritin

Mice lacking ferritin H in cardiomyocytes were feeded these mice a high-iron diet

SLC7A11-mediated ferroptosis causes cardiomyopathy from cardiac ferritin H loss

[109]

Iron transport and utilization

FPN1

Sulforaphane-treated STZ-induced diabetic rats with cardiac IRI models

Activation of NRF2/FPN1 pathway attenuates myocardial ischemia–reperfusion injury in diabetic rats by regulating iron homeostasis and ferroptosis

[65]

Glucose and hypoxia/reoxygenation-induced cardiomyocytes injury models treated with erastin in vitro

Frataxin

Cardiomyocyte-specific HIF-1α knockout mice

Frataxin, an iron storage protein under hypoxia, prevented mitochondrial iron overload and ROS and preserved cardiomyocyte membrane integrity

[110]

Iron homeostasis regulation

Hepcidin

Neonatal mice with apical resection-induced heart regeneration

Macrophages lacking hepcidin promoted cardiomyocyte proliferation

[111]

IL-6 increased hepcidin in inflammatory macrophages

STAT3

Hepcidin deficiency phosphorylated STAT3, releasing IL-4 and IL-13

HIF

Cardiomyocyte-specific HIF-1α knockout mice

HIF-1α-frataxin signaling protects against hypoxia/ischemia

[110]