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Role of iron homeostasis in the heart

Heart failure, cardiomyopathy, and ischemia–reperfusion injury

Bedeutung der Eisenhomöostase im Herzen

Herzinsuffizienz, Kardiomyopathie und Ischämie-Reperfusions-Schaden

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Abstract

As an essential trace mineral in mammals and the second most abundant metal in the Earth’s crust, iron acts as a double-edged sword in humans. Iron plays important beneficial roles in numerous biological processes ranging from deoxyribonucleic acid biosynthesis and protein function to cell cycle progression. However, iron metabolism disruption leads to widespread tissue degeneration and organ dysfunction. An increasing number of studies have focused on iron regulation pathways and have explored the relationship between iron and cardiovascular diseases. Ferroptosis, an iron-dependent form of programmed cell death, was first described in cancer cells and has recently been linked to heart diseases, including cardiac ischemia–reperfusion injury and doxorubicin-induced myocardiopathy. Here, we summarize recent advances in our understanding of iron homeostasis and heart diseases and discuss potential relationships between ferroptosis and cardiac ischemia–reperfusion injury and cardiomyopathy.

Zusammenfassung

Als essenzielles Spurenelement bei Säugetieren und als zweithäufigstes Metall in der Erdkruste ist Eisen ein zweischneidiges Schwert für den Menschen. Eisen spielt eine wichtige nützliche Rolle in zahlreichen biologischen Prozessen von der Biosynthese der Desoxyribonukleinsäure und der Proteinfunktion bis zum Ablauf des Zellzyklus. Jedoch führt eine Störung des Eisenstoffwechsels zu einer ausgedehnten Gewebedegeneration und Organfunktionsstörungen. Eine zunehmende Zahl von Studien hat die Signalwege der Eisenregulation in den Fokus genommen und den Zusammenhang zwischen Eisen und Herz-Kreislauf-Erkrankungen untersucht. Ferroptose, eine eisenabhängige Form des programmierten Zelltods, wurde zuerst bei Krebszellen beschrieben und ist erst kürzlich mit Herzkrankheiten, einschließlich des kardialen Ischämie-Reperfusions-Schadens und der durch Doxorubicin induzierten Myokardiopathie, in Verbindung gebracht. Im vorliegenden Beitrag werden die aktuellen Fortschritte im Verständnis von Eisenhomöostase und Herzerkrankungen zusammengefasst sowie mögliche Zusammenhänge zwischen Ferroptose und kardialem Ischämie-Reperfusions-Schaden sowie Kardiomyopathie erörtert.

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References

  1. Kerins MJ, Ooi A (2018) The roles of NRF2 in modulating cellular iron homeostasis. Antioxid Redox Signal 29(17):1756–1773. https://doi.org/10.1089/ars.2017.7176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Ganz T, Nemeth E (2012) Hepcidin and iron homeostasis. Biochim Biophys Acta 1823(9):1434–1443. https://doi.org/10.1016/j.bbamcr.2012.01.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Valko M, Jomova K, Rhodes CJ, Kuc K (2016) Redox- and non-redox-metal-induced formation of free radicals and their role in human disease. Arch Toxicol. https://doi.org/10.1007/s00204-015-1579-5

    Article  PubMed  Google Scholar 

  4. Eaton JW, Qian M (2002) Molecular bases of cellular iron toxicity. Free Radic Biol Med 32(9):833–840. https://doi.org/10.1016/S0891-5849(02)00772-4

    Article  CAS  PubMed  Google Scholar 

  5. Galesloot TE et al (2015) Iron and hepcidin as risk factors in atherosclerosis: what do the genes say? BMC Genet 16(1):1–12. https://doi.org/10.1186/s12863-015-0246-4

    Article  CAS  Google Scholar 

  6. Lam CSP et al (2018) Iron deficiency in chronic heart failure: case-based practical guidance. ESC Heart Fail 5(5):764–771. https://doi.org/10.1002/ehf2.12333

    Article  PubMed  PubMed Central  Google Scholar 

  7. Chang H, Shapiro JS, Ardehali H (2016) Getting to the ‘heart’ of cardiac disease by decreasing mitochondrial iron. Circ Res. https://doi.org/10.1161/CIRCRESAHA.116.309746

    Article  PubMed  PubMed Central  Google Scholar 

  8. Gammella E, Recalcati S, Rybinska I, Buratti P, Cairo G (2015) Iron-induced damage in cardiomyopathy: oxidative-dependent and independent mechanisms. Oxid Med Cell Longev 2015:1–10. https://doi.org/10.1155/2015/230182

    Article  Google Scholar 

  9. Lawen A, Lane DJR (2013) Mammalian iron homeostasis in health and disease: uptake, storage, transport, and molecular mechanisms of action. Antioxid Redox Signal 18(18):2473–2507. https://doi.org/10.1089/ars.2011.4271

    Article  CAS  PubMed  Google Scholar 

  10. Kassam Z, Moayyedi P, Crowther M (2012) Iron overload in human disease. N Engl J Med 366(16):1549. https://doi.org/10.1056/NEJMra1004967

    Article  PubMed  Google Scholar 

  11. Zimmermann MB, Hurrell RF (2007) Nutritional iron deficiency. Lancet 370(9586):511–520. https://doi.org/10.1016/S0140-6736(07)61235-5

    Article  CAS  PubMed  Google Scholar 

  12. Zhang H, Zhabyeyev P, Wang S, Oudit GY (2019) Role of iron metabolism in heart failure: from iron deficiency to iron overload. Biochim Biophys Acta 1865(7):1925–1937. https://doi.org/10.1016/j.bbadis.2018.08.030

    Article  CAS  Google Scholar 

  13. Das SK et al (2015) Iron-overload injury and cardiomyopathy in acquired and genetic models is attenuated by resveratrol therapy. Sci Rep 5:1–15. https://doi.org/10.1038/srep18132

    Article  CAS  Google Scholar 

  14. Chang H‑C et al (2016) Reduction in mitochondrial iron alleviates cardiac damage during injury. EMBO Mol Med 8(3):247–267. https://doi.org/10.15252/emmm.201505748

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Djulbegovic MB, Uversky VN (2019) Ferroptosis—an iron- and disorder-dependent programmed cell death. Int J Biol Macromol 135:1052–1069. https://doi.org/10.1016/j.ijbiomac.2019.05.221

    Article  CAS  PubMed  Google Scholar 

  16. Cao JY, Dixon SJ (2016) Mechanisms of ferroptosis. Cell Mol Life Sci 73(11–12):2195–2209. https://doi.org/10.1007/s00018-016-2194-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Fang X et al (2019) Ferroptosis as a target for protection against cardiomyopathy. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1821022116

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fang X et al (2020) Loss of cardiac ferritin H facilitates cardiomyopathy via Slc7a11-mediated ferroptosis. Circ Res. https://doi.org/10.1161/circresaha.120.316509

    Article  PubMed  PubMed Central  Google Scholar 

  19. Han O (2011) Molecular mechanism of intestinal iron absorption. Metallomics 3(2):103–109. https://doi.org/10.1039/c0mt00043d

    Article  CAS  PubMed  Google Scholar 

  20. Anderson GJ, Frazer DM (2017) Current understanding of iron homeostasis. Am J Clin Nutr 106:1559S–1566S. https://doi.org/10.3945/ajcn.117.155804

    Article  PubMed  PubMed Central  Google Scholar 

  21. Beaumont C, Nicolas G, Vaulont S (2003) Hepcidin, a key regulator of iron metabolism. Hematologie 9(1):27–36

    CAS  Google Scholar 

  22. Beinert H, Holm RH, Münck E (1997) Iron-sulfur clusters: nature’s modular, multipurpose structures. Science 277(5326):653–659. https://doi.org/10.1126/science.277.5326.653

    Article  CAS  PubMed  Google Scholar 

  23. Young SP, Roberts S, Bomford A (1985) Intracellular processing of transferrin and iron by isolated rat hepatocytes. Biochem J 232(3):819–823. https://doi.org/10.1042/bj2320819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Theil EC (2013) Ferritin: the protein nanocage and iron biomineral in health and in disease. Inorg Chem 52(21):12223–12233. https://doi.org/10.1021/ic400484n

    Article  CAS  PubMed  Google Scholar 

  25. Truman-Rosentsvit M et al (2018) Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood 131(3):342–352. https://doi.org/10.1182/blood-2017-02-768580

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Huang ML‑H, Lane DJR, Richardson DR (2011) Mitochondrial mayhem: the mitochondrion as a modulator of iron metabolism and its role in disease. Antioxid Redox Signal 15(12):3003–3019. https://doi.org/10.1089/ars.2011.3921

    Article  CAS  PubMed  Google Scholar 

  27. Santambrogio P, Biasiotto G, Sanvito F, Olivieri S, Arosio P, Levi S (2007) Mitochondrial ferritin expression in adult mouse tissues. J Histochem Cytochem 55(11):1129–1137. https://doi.org/10.1369/jhc.7A7273.2007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wu WS et al (2013) Mitochondrial ferritin attenuates β‑amyloid-induced neurotoxicity: reduction in oxidative damage through the Erk/P38 mitogen-activated protein kinase pathways. Antioxidants Redox Signal 18(2):158–169. https://doi.org/10.1089/ars.2011.4285

    Article  CAS  Google Scholar 

  29. Paterek A, Mackiewicz U, Mączewski M (2018) Iron and the heart: a paradigm shift from systemic to cardiomyocyte abnormalities. J Cell Physiol. https://doi.org/10.1002/jcp.28820

    Article  Google Scholar 

  30. Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC (2015) Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Rep 13(3):533–545. https://doi.org/10.1016/j.celrep.2015.09.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Hentze MW, Muckenthaler MU, Galy B, Camaschella C (2010) Two to tango: regulation of mammalian iron metabolism. Cell 142(1):24–38. https://doi.org/10.1016/j.cell.2010.06.028

    Article  CAS  PubMed  Google Scholar 

  32. Illing AC, Shawki A, Cunningham CL, Mackenzie B (2012) Substrate profile and metal-ion selectivity of human divalent metal-ion transporter‑1. J Biol Chem 287(36):30485–30496. https://doi.org/10.1074/jbc.M112.364208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shawki A et al (2015) Intestinal DMT1 is critical for iron absorption in the mouse but is not required for the absorption of copper or manganese. Am J Physiol Gastrointest Liver Physiol 309(8):G635–G647. https://doi.org/10.1152/ajpgi.00160.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ke Y et al (2003) Post-transcriptional expression of DMT1 in the heart of rat. J Cell Physiol 196(1):124–130. https://doi.org/10.1002/jcp.10284

    Article  CAS  PubMed  Google Scholar 

  35. Zamponi GW, Striessnig J, Koschak A, Dolphin AC (2015) The physiology, pathology, and pharmacology of voltage-gated calcium channels and their future therapeutic potential. Pharmacol Rev 67(4):821–870. https://doi.org/10.1124/pr.114.009654

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Tsushima RG, Wickenden AD, Bouchard RA, Oudit GY, Liu PP, Backx PH (1999) Modulation of iron uptake in heart by L‑type Ca2+ channel modifiers: possible implications in iron overload. Circ Res 84(11):1302–1309. https://doi.org/10.1161/01.RES.84.11.1302

    Article  CAS  PubMed  Google Scholar 

  37. Lemaire R et al (2011) Iron-overload decreases Cav1.3-dependent L‑type Ca2+ currents leading to bradycardia, altered electrical conduction and atrial fibrillation. Circ Arrhythm Electrophysiol 130(6):1514–1523. https://doi.org/10.1038/jid.2010.15.Antagonistic

    Article  Google Scholar 

  38. Kumfu S et al (2018) Combined iron chelator and T‑type calcium channel blocker exerts greater efficacy on cardioprotection than monotherapy in iron-overload thalassemic mice. Eur J Pharmacol 822:43–50. https://doi.org/10.1016/j.ejphar.2018.01.015

    Article  CAS  PubMed  Google Scholar 

  39. Sadaf A, Hasan B, Das JK, Colan S, Alvi N (2018) Calcium channel blockers for preventing cardiomyopathy due to iron overload in people with transfusion-dependent beta thalassaemia. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD011626.pub2

    Article  PubMed  PubMed Central  Google Scholar 

  40. Sato T et al (2018) mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function. Proc Natl Acad Sci U S A 115(27):E6291–E6300. https://doi.org/10.1073/pnas.1804701115

    Article  PubMed  PubMed Central  Google Scholar 

  41. Haddad S et al (2017) Iron-regulatory proteins secure iron availability in cardiomyocytes to prevent heart failure. Eur Heart J 38(5):362–372. https://doi.org/10.1093/eurheartj/ehw333

    Article  CAS  PubMed  Google Scholar 

  42. Drakesmith H, Nemeth E, Ganz T (2015) Ironing out Ferroportin. Cell Metab 22(5):777–787. https://doi.org/10.1016/j.cmet.2015.09.00

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lakhal-Littleton S et al (2016) An essential cell-autonomous role for hepcidin in cardiac iron homeostasis. Elife 5:1–25. https://doi.org/10.7554/eLife.19804

    Article  Google Scholar 

  44. Lakhal-littleton S et al (2015) Cardiac ferroportin regulates cellular iron homeostasis and is important for cardiac function. Proc Natl Acad Sci USA. https://doi.org/10.1073/pnas.1422373112

    Article  PubMed  PubMed Central  Google Scholar 

  45. Bolotta A et al (2019) New insights into the hepcidin-ferroportin axis and iron homeostasis in iPSC-derived cardiomyocytes from Friedreich’s ataxia patient. Oxid Med Cell Longev. https://doi.org/10.1155/2019/7623023

    Article  PubMed  PubMed Central  Google Scholar 

  46. Merle U, Fein E, Gehrke SG, Stremmel W, Kulaksiz H (2007) The iron regulatory peptide hepcidin is expressed in the heart and regulated by hypoxia and inflammation. Endocrinology 148(6):2663–2668. https://doi.org/10.1210/en.2006-1331

    Article  CAS  PubMed  Google Scholar 

  47. Isoda M et al (2010) Expression of the peptide hormone hepcidin increases in cardiomyocytes under myocarditis and myocardial infarction. J Nutr Biochem 21(8):749–756. https://doi.org/10.1016/j.jnutbio.2009.04.009

    Article  CAS  PubMed  Google Scholar 

  48. Simonis G et al (2010) The iron-regulatory peptide hepcidin is upregulated in the ischemic and in the remote myocardium after myocardial infarction. Peptides 31(9):1786–1790. https://doi.org/10.1016/j.peptides.2010.05.013

    Article  CAS  PubMed  Google Scholar 

  49. Sukumaran A, Chang J, Han M, Mintri S, Khaw BA, Kim J (2017) Iron overload exacerbates age-associated cardiac hypertrophy in a mouse model of hemochromatosis. Sci Rep 7(1):1–10. https://doi.org/10.1038/s41598-017-05810-2

    Article  CAS  Google Scholar 

  50. Shapiro JS, Chang H, Ardehali H (2017) Iron and sex cross paths in the heart. J Am Heart Assoc. https://doi.org/10.1161/JAHA.116.005459

    Article  PubMed  PubMed Central  Google Scholar 

  51. Ezekowitz JA, McAlister FA, Armstrong PW (2003) Anemia is common in heart failure and is associated with poor outcomes: insights from a cohort of 12 065 patients with new-onset heart failure. Circulation 107(2):223–225. https://doi.org/10.1161/01.CIR.0000052622.51963.FC

    Article  PubMed  Google Scholar 

  52. Opasich C et al (2005) Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 26(21):2232–2237. https://doi.org/10.1093/eurheartj/ehi388

    Article  CAS  PubMed  Google Scholar 

  53. McDonagh T et al (2018) Screening, diagnosis and treatment of iron deficiency in chronic heart failure: putting the 2016 European society of cardiology heart failure guidelines into clinical practice. Eur J Heart Fail 20(12):1664–1672. https://doi.org/10.1002/ejhf.1305

    Article  CAS  PubMed  Google Scholar 

  54. Jankowska EA, von Haehling S, Anker SD, MacDougall IC, Ponikowski P (2013) Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives. Eur Heart J 34(11):816–826. https://doi.org/10.1093/eurheartj/ehs224

    Article  CAS  PubMed  Google Scholar 

  55. Jankowska EA et al (2014) Iron deficiency defined as depleted iron stores accompanied by unmet cellular iron requirements identifies patients at the highest risk of death after an episode of acute heart failure. Eur Heart J 35(36):2468–2476. https://doi.org/10.1093/eurheartj/ehu235

    Article  CAS  PubMed  Google Scholar 

  56. Sportouch L et al (2019) Dynamic iron status after acute heart failure. Arch Cardiovasc Dis. https://doi.org/10.1016/j.acvd.2019.02.002

    Article  PubMed  Google Scholar 

  57. Kobak KA et al (2019) Structural and functional abnormalities in iron-depleted heart. Heart Fail Rev 24(2):269–277. https://doi.org/10.1007/s10741-018-9738-4

    Article  CAS  PubMed  Google Scholar 

  58. Melenovsky V et al (2016) Myocardial iron content and mitochondrial function in human heart failure : a direct tissue analysis. Eur J Heart Fail. https://doi.org/10.1002/ejhf.640

    Article  PubMed  Google Scholar 

  59. Powell LW, Subramaniam VN, Yapp TR (2000) Haemochromatosis in the new millennium. J Hepatol 32(1):48–62. https://doi.org/10.1016/S0168-8278(00)80415-8

    Article  CAS  PubMed  Google Scholar 

  60. Radford-Smith DE, Powell EE, Powell LW (2018) Haemochromatosis: a clinical update for the practising physician. Intern Med J 48(5):509–516. https://doi.org/10.1111/imj.13784

    Article  CAS  PubMed  Google Scholar 

  61. Aldouri MA et al (1990) High incidence of cardiomyopathy in beta-thalassaemia patients receiving regular transfusion and iron chelation: reversal by intensified chelation. Acta Haematol 84(3):113–117. https://doi.org/10.1159/000205046

    Article  CAS  PubMed  Google Scholar 

  62. Horwitz LD, Rosenthal EA (1999) Iron-mediated cardiovascular injury. Vasc Med 4(2):93–99. https://doi.org/10.1191/135886399676588477

    Article  CAS  PubMed  Google Scholar 

  63. Siri-Angkul N, Xie L, Chattipakorn SC, Myles RC (2018) Cellular electrophysiology of iron-overload cardiomycytes. Front Physiol 9:1–7. https://doi.org/10.3389/fphys.2018.01615

    Article  Google Scholar 

  64. Thein SL (2013) The molecular basis of β‑thalassemia. Cold Spring Harb Perspect Med 3(5):1–24. https://doi.org/10.1101/cshperspect.a011700

    Article  CAS  Google Scholar 

  65. de Montalembert M et al (2017) Cardiac iron overload in chronically transfused patients with thalassemia, sickle cell anemia, or myelodysplastic syndrome. PLoS ONE 12(3):1–12. https://doi.org/10.1371/journal.pone.0172147

    Article  CAS  Google Scholar 

  66. Huang Y et al (2019) Imbalance of erythropoiesis and iron metabolism in patients with thalassemia. Int J Med Sci 16(2):302–310. https://doi.org/10.7150/ijms.27829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Lockshin RA, Williams CM (1965) Programmed cell death‑I. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth. J Insect Physiol 11(2):123–126

    Article  CAS  PubMed  Google Scholar 

  68. Yang G, Sau C, Lai W, Cichon J, Li W (2015) Live to die another way: modes of programmed cell death and the signals emanating from dying cells. Nat Rev Mol Cell Biol 344(6188):1173–1178. https://doi.org/10.1126/science.1249098.Sleep

    Article  Google Scholar 

  69. Vostinar AE, Goldsby HJ, Ofria C (2019) Suicidal selection: programmed cell death can evolve in unicellular organisms due solely to kin selection. Ecol Evol. https://doi.org/10.1002/ece3.5460

    Article  PubMed  PubMed Central  Google Scholar 

  70. Yao Y, Lu Q, Hu Z, Yu Y, Chen Q, Wang QK (2017) A non-canonical pathway regulates ER stress signaling and blocks ER stress-induced apoptosis and heart failure. Nat Commun. https://doi.org/10.1038/s41467-017-00171-w

    Article  PubMed  PubMed Central  Google Scholar 

  71. Maejima Y, Isobe M, Sadoshima J (2016) Regulation of autophagy by Beclin 1 in the heart. J Mol Cell Cardiol 95:19-25. https://doi.org/10.1016/j.yjmcc.2015.10.032

    Article  CAS  PubMed  Google Scholar 

  72. Davies (2012) Mechanisms of cell death in heart disease. Arterioscler Thromb Vasc Biol. https://doi.org/10.1161/ATVBAHA.111.224915

    Article  PubMed  PubMed Central  Google Scholar 

  73. Naveenkumar SK, Sharathbabu BN, Hemshekhar M, Kemparaju K, Girish KS, Mugesh G (2018) The role of reactive oxygen species and ferroptosis in heme-mediated activation of human platelets. ACS Chem Biol 13(8):1996–2002. https://doi.org/10.1021/acschembio.8b00458

    Article  CAS  PubMed  Google Scholar 

  74. Xie Y et al (2016) Ferroptosis : process and function. Cell Death Differ 23:369–379. https://doi.org/10.1038/cdd.2015.158

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Weiland A et al (2018) Ferroptosis and its role in diverse brain diseases. Mol Neurobiol. https://doi.org/10.1007/s12035-018-1403-3

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chen WCW et al (2016) Ferroptosis: a regulated cell death nexus linking metabolism, redox biology, and disease. Cell 33(2):557–573. https://doi.org/10.1002/stem.1868.Human

    Article  Google Scholar 

  77. Dixon SJ et al (2014) Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife 3:1–25. https://doi.org/10.7554/eLife.02523

    Article  CAS  Google Scholar 

  78. Yagoda N et al (2007) RAS-RAF-MEK-dependent oxidative cell death involving voltage-dependent anion channels. Nature 447(7146):864–868. https://doi.org/10.1038/nature05859

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Kim JY et al (2001) Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. Biochim Biophys Acta 1512(2):335–344. https://doi.org/10.1016/S0005-2736(01)00338-8

    Article  CAS  PubMed  Google Scholar 

  80. Am P, Heart JP, Physiol C (2017) Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes. Am J Physiol Heart Circ Physiol. https://doi.org/10.1152/ajpheart.00452.2017

    Article  Google Scholar 

  81. Baseler WA et al (2013) Reversal of mitochondrial proteomic loss in type 1 diabetic heart with overexpression of phospholipid hydroperoxide glutathione peroxidase. Am J Physiol Regul Integr Comp Physiol. https://doi.org/10.1152/ajpregu.00249.2012

    Article  PubMed  PubMed Central  Google Scholar 

  82. Dabkowski ER, Williamson CL, Hollander JM (2008) Mitochondria-specific transgenic overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion-associated cardiac dysfunction. Free Radic Biol Med 45(6):855–865. https://doi.org/10.1016/j.freeradbiomed.2008.06.021

    Article  CAS  PubMed  Google Scholar 

  83. Del Re DP, Amgalan D, Linkermann A, Liu Q, Kitsis RN (2019) Fundamental mechanisms of regulated cell death and implications for heart disease. Physiol Rev 99(4):1765–1817. https://doi.org/10.1152/physrev.00022.2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Aoyagi T et al (2012) Cardiac mTOR protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 303(1):75–85. https://doi.org/10.1152/ajpheart.00241.2012

    Article  CAS  Google Scholar 

  85. Song X et al (2010) mTOR attenuates the inflammatory response in cardiomyocytes and prevents cardiac dysfunction in pathological hypertrophy. Am J Physiol, Cell Physiol 299(6):1250–1252. https://doi.org/10.1152/ajpcell.00338.2010

    Article  CAS  Google Scholar 

  86. Bayeva M et al (2012) MTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab 16(5):645–657. https://doi.org/10.1016/j.cmet.2012.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Chiang SK, Chen SE, Chang LC (2019) A dual role of heme oxygenase‑1 in cancer cells. Int J Mol Sci 20(1):1–18. https://doi.org/10.3390/ijms20010039

    Article  CAS  Google Scholar 

  88. Dixon SJ et al (2012) Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell 149(5):1060–1072. https://doi.org/10.1016/j.cell.2012.03.042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ma S, Henson ES, Chen Y, Gibson SB (2016) Ferroptosis is induced following siramesine and lapatinib treatment of breast cancer cells. Cell Death Dis 7(7):1–11. https://doi.org/10.1038/cddis.2016.208

    Article  CAS  Google Scholar 

  90. Hou W et al (2016) Autophagy promotes ferroptosis by degradation of ferritin. Autophagy 12(8):1425–1428. https://doi.org/10.1080/15548627.2016.1187366

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Boya P, Kroemer G (2008) Lysosomal membrane permeabilization in cell death. Oncogene 27(50):6434–6451. https://doi.org/10.1038/onc.2008.310

    Article  CAS  PubMed  Google Scholar 

  92. Gaschler MM, Stockwell BR (2017) Lipid peroxidation in cell death. Biochem Biophys Res Commun 482(3):419–425. https://doi.org/10.1016/j.bbrc.2016.10.086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Magtanong L, Ko PJ, Dixon SJ (2016) Emerging roles for lipids in non-apoptotic cell death. Cell Death Differ 23(7):1099–1109. https://doi.org/10.1038/cdd.2016.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Bhimaraj A, Tang WHW (2012) Role of oxidative stress in disease progression in stage B, a pre-cursor of heart failure. Heart Fail Clin 8(1):101–111. https://doi.org/10.1016/j.hfc.2011.08.003

    Article  PubMed  Google Scholar 

  95. Higdon A, Diers AR, Oh JY, Landar A, Darley-Usmar VM (2012) Cell signalling by reactive lipid species: new concepts and molecular mechanisms. Biochem J 442(3):453–464. https://doi.org/10.1042/BJ20111752

    Article  CAS  PubMed  Google Scholar 

  96. Agmon E, Stockwell BR (2017) Lipid homeostasis and regulated cell death. Curr Opin Chem Biol 39:83–89. https://doi.org/10.1016/j.cbpa.2017.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by Natural Science Foundation of Zhejiang Province, Grant No: LY16H020008

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  1. Department of Cardiology, Key Laboratory of Cardiovascular Intervention and Regenerative Medicine of Zhejiang Province, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Zhejiang, Hangzhou, China

    Hangying Ying, Zhida Shen, Jiacheng Wang & Binquan Zhou

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  1. Hangying Ying
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  2. Zhida Shen
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  3. Jiacheng Wang
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Correspondence to Binquan Zhou.

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H. Ying, Z. Shen, J. Wang and B. Zhou declare that they have no competing interests.

For this article no studies with human participants or animals were performed by any of the authors. All studies performed were in accordance with the ethical standards indicated in each case.

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Ying, H., Shen, Z., Wang, J. et al. Role of iron homeostasis in the heart. Herz 47, 141–149 (2022). https://doi.org/10.1007/s00059-021-05039-w

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