L-type Ca2+ channels provide a major pathway for iron entry into cardiomyocytes in iron-overload cardiomyopathy
Abstract
Under conditions of iron overload, which are now reaching epidemic proportions worldwide, iron-overload cardiomyopathy is the most important prognostic factor in patient survival. We hypothesize that in iron-overload disorders, iron accumulation in the heart depends on ferrous iron (Fe2+) permeation through the L-type voltage-dependent Ca2+ channel (LVDCC), a promiscuous divalent cation transporter. Iron overload in mice was associated with increased mortality, systolic and diastolic dysfunction, bradycardia, hypotension, increased myocardial fibrosis and elevated oxidative stress. Treatment with LVDCC blockers (CCBs; amlodipine and verapamil) at therapeutic levels inhibited the LVDCC current in cardiomyocytes, attenuated myocardial iron accumulation and oxidative stress, improved survival, prevented hypotension and preserved heart structure and function. Consistent with the role of LVDCCs in myocardial iron uptake, iron-overloaded transgenic mice with cardiac-specific overexpression of the LVDCC alpha1-subunit had twofold higher myocardial iron and oxidative stress levels, as well as greater impairment in cardiac function, compared with littermate controls; LVDCC blockade was again protective. Our results indicate that cardiac LVDCCs are key transporters of iron into cardiomyocytes under iron-overloaded conditions, and potentially represent a new therapeutic target to reduce the cardiovascular burden from iron overload.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The clinical severity of hemochromatosis is related to NTBI, a toxic iron species bound to low molecular weight molecules, easily taken up by hepatocytes and pancreatic cells via ZIP14 transporter and by cardiomyocytes through other transporters.
“The clinical severity of hemochromatosis is related to NTBI, a toxic iron species bound to low molecular weight molecules, easily taken up by hepatocytes and pancreatic cells via ZIP14 transporter82 and by cardiomyocytes through other transporters.83”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [83]
Aside from L-type calcium channels, which have some iron carrying capability, no compelling candidates have been identified that transport iron atoms directly into cells.
“However, aside from L-type calcium channels, which have some iron carrying capability, 73 no compelling candidates have been identified that transport iron atoms directly into cells.”
From Forging a field: the golden age of iron biology. (2008) · cites this paper as [73]
Cites
Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes
Esterbauer, H., Schaur, R. J., & Zollner, H. (1991) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(91)90192-6 · Cited by 6,672 · see citing works
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
Gunshin, H., Mackenzie, B., Berger, U. V., Gunshin, Y., Romero, M. F., Boron, W. F., Nussberger, S., Gollan, J. L., & Hediger, M. A. (1997) · Nature · doi:10.1038/41343 · Cited by 3,166 · see citing works
Structure and Regulation of Voltage-Gated Ca <sup>2+</sup> Channels
Catterall, W. A. (2000) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.16.1.521 · Cited by 2,344 · see citing works
Andrews, N. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199912233412607 · Cited by 2,130 · see citing works
Inherited haemoglobin disorders: an increasing global health problem.
Weatherall, D. J., & Clegg, J. B. (2001) · Europe PMC (PubMed Central) · Cited by 1,159 · see citing works
An iron-regulated ferric reductase associated with the absorption of dietary iron
McKie, A. T., Barrow, D., Latunde-Dada, G. O., Rolfs, A., Sager, G., Mudaly, E., Mudaly, M., Richardson, C., Barlow, D., Bomford, A., et al. (2001) · Science · doi:10.1126/science.1057206 · Cited by 1,101 · see citing works
Survival and Causes of Death in Cirrhotic and in Noncirrhotic Patients with Primary Hemochromatosis
Niederau, C., Fischer, R., Sonnenberg, A., Stremmel, W., Trampisch, H. J., & Strohmeyer, G. W. (1985) · New England Journal of Medicine · doi:10.1056/nejm198511143132004 · Cited by 1,063 · see citing works
Long-term survival in patients with hereditary hemochromatosis
Niederau, C., Fischer, R., Pürschel, A., Stremmel, W., Häussinger, D., & Strohmeyer, G. W. (1996) · Gastroenterology · doi:10.1053/gast.1996.v110.pm8613000 · Cited by 885 · see citing works
Survival in Medically Treated Patients with Homozygous β-Thalassemia
Olivieri, N. F., Nathan, D. G., MacMillan, J. H., Wayne, A. S., Liu, P. P., McGee, A., Martin, M., Koren, G., & Cohen, A. R. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409013310903 · Cited by 842 · see citing works
Self-citationBrittenham, G. M., Griffith, P. M., Nienhuis, A. W., McLaren, C. E., Young, N. S., Tucker, E. E., Allen, C. J., Farrell, D. E., & Harris, J. W. (1994) · New England Journal of Medicine · doi:10.1056/nejm199409013310902 · Cited by 822 · see citing works
Olivieri, N. F. (1999) · New England Journal of Medicine · doi:10.1056/nejm199907083410207 · Cited by 718 · see citing works
Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias
Weatherall, D. J. (2001) · Nature Reviews Genetics · doi:10.1038/35066048 · Cited by 692 · see citing works
SURVIVAL AND CAUSES OF DEATH IN THALASSAEMIA MAJOR
Zurlo, M., Stefano, P. D., Borgna‐Pignatti, C., Palma, A. D., Melevendi, C., Piga, A. G., Gregorio, F. D., Mg, B., & Terzoli, S. (1989) · The Lancet · doi:10.1016/s0140-6736(89)90264-x · Cited by 607 · see citing works
Survival in β-thalassaemia major in the UK: data from the UK Thalassaemia Register
Modell, B., Khan, M., & Darlison, M. W. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02357-6 · Cited by 587 · see citing works
Regulation of Myocardial Contractility and Cell Size by Distinct PI3K-PTEN Signaling Pathways
Crackower, M. A., Oudit, G. Y., Kozieradzki, I., Sarao, R., Sun, H., Sasaki, T., Hirsch, E., Suzuki, A., Shioi, T., Irie-Sasaki, J., et al. (2002) · Cell · doi:10.1016/s0092-8674(02)00969-8 · Cited by 576 · see citing works
Self-citationHaem oxygenase-1 prevents cell death by regulating cellular iron
Ferris, C. D., Jaffrey, S. R., Sawa, A., Takahashi, M., Brady, S. D., Barrow, R. K., Tysoe, S. A., Wolosker, H., Barañano, D. E., Doré, S., et al. (1999) · Nature Cell Biology · doi:10.1038/11072 · Cited by 509 · see citing works
Buja, L. M., & Roberts, W. C. (1971) · The American Journal of Medicine · doi:10.1016/0002-9343(71)90240-3 · Cited by 475 · see citing works
Abernethy, D. R., & Schwartz, J. B. (1999) · New England Journal of Medicine · doi:10.1056/nejm199911043411907 · Cited by 440 · see citing works
Vitamin C-Induced Decomposition of Lipid Hydroperoxides to Endogenous Genotoxins
Lee, S. H., Oe, T., & Blair, I. A. (2001) · Science · doi:10.1126/science.1059501 · Cited by 416 · see citing works
Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells
Wang, S., Song, L., Lakatta, E. G., & Cheng, H. (2001) · Nature · doi:10.1038/35069083 · Cited by 407 · see citing works
Iron-dependent regulation of the divalent metal ion transporter
Gunshin, H., Allerson, C. R., Polycarpou-Schwarz, M., Rofts, A., Rogers, J. T., Kishi, F., Hentze, M. W., Rouault, T. A., Andrews, N. C., & Hediger, M. A. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03189-1 · Cited by 305 · see citing works
Livrea, M., Tesoriere, L., Pintaudi, A., Calabrese, A., Maggio, A., Freisleben, H., D’Arpa, D., D'Anna, R., & Bongiorno, A. (1996) · Blood · doi:10.1182/blood.v88.9.3608.bloodjournal8893608 · Cited by 274 · see citing works
Thalassemia — a global public health problem
Weatherall, D. J., & Clegg, J. B. (1996) · Nature Medicine · doi:10.1038/nm0896-847 · Cited by 253 · see citing works
Luo, X. P., Yazdanpanah, M., Bhooi, N., & Lehotay, D. C. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1353 · Cited by 191 · see citing works
Self-citationLeft ventricular diastolic Doppler characteristics in beta-thalassemia major.
Kremastinos, D. T., Tsiapras, D. P., Tsetsos, G. A., Rentoukas, E. I., Vretou, H. P., & TOUTOUZAS, P. K. (1993) · Circulation · doi:10.1161/01.cir.88.3.1127 · Cited by 180 · see citing works
Chaston, T. B., & Richardson, D. R. (2003) · American Journal of Hematology · doi:10.1002/ajh.10348 · Cited by 168 · see citing works
Modulation of Iron Uptake in Heart by L-Type Ca2+Channel Modifiers
Tsushima, R. G., Wickenden, A. D., Bouchard, R. A., Oudit, G. Y., Liu, P. P., & Backx, P. H. (1999) · Circulation Research · doi:10.1161/01.res.84.11.1302 · Cited by 157 · see citing works
Self-citationIron overload cardiomyopathies: New insights into an old disease
Liu, P. J., & Olivieri, N. F. (1994) · Cardiovascular Drugs and Therapy · doi:10.1007/bf00877096 · Cited by 154 · see citing works
Self-citationThe ENCORE Investigators (2003) · Circulation · doi:10.1161/01.cir.0000046488.52939.bf · Cited by 154 · see citing works
Iron overload is a determinant of morbidity and mortality in adult patients with sickle cell disease
Ballas, S. K. (2001) · Seminars in Hematology · doi:10.1016/s0037-1963(01)90058-7 · Cited by 148 · see citing works
Heart cells in culture: a model of myocardial iron overload and chelation.
Link, G., Pinson, A., & Hershko, C. (1985) · PubMed · Cited by 141 · see citing works
Myocarditis in β-Thalassemia Major
Kremastinos, D. T., Tiniakos, G., THEODORAKIS, G. N., Katritsis, D. G., & TOUTOUZAS, P. K. (1995) · Circulation · doi:10.1161/01.cir.91.1.66 · Cited by 129 · see citing works
Randell, E. W., Parkes, J. G., Olivieri, N. F., & Templeton, D. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33971-6 · Cited by 127 · see citing works
Antioxidant properties of calcium antagonists related to membrane biophysical interactions
Mason, R. P., Mak, I. T., Trumbore, M. W., & Mason, P. E. (1999) · The American Journal of Cardiology · doi:10.1016/s0002-9149(99)00360-4 · Cited by 119 · see citing works
Antioxidant status and lipid peroxidation in hereditary haemochromatosis
Young, I. S., Trouton, T. G., Torney, J. J., McMaster, D., Callender, M. E., & Trimble, E. R. (1994) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(94)90041-8 · Cited by 115 · see citing works
Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex
Cohn, R. D., Durbeej, M., Moore, S. A., Coral‐Vázquez, R. M., Prouty, S. J., & Campbell, K. P. (2001) · Journal of Clinical Investigation · doi:10.1172/jci11642 · Cited by 113 · see citing works
Genetic regulation of cell function in response to iron overload or chelation
Templeton, D. M., & Liu, Y. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00497-x · Cited by 111 · see citing works
Metal transporters and disease
Andrews, N. C. (2002) · Current Opinion in Chemical Biology · doi:10.1016/s1367-5931(02)00307-1 · Cited by 110 · see citing works
Effects of grapefruit juice and smoking on verapamil concentrations in steady state
Fuhr, U., Müller-Peltzer, H., Kern, R., Lopez-Rojas, P., Jünemann, M., Harder, S., & Staib, H. A. (2002) · European Journal of Clinical Pharmacology · doi:10.1007/s00228-002-0436-7 · Cited by 97 · see citing works
Recent advances in disorders of iron metabolism: mutations, mechanisms and modifiers
Roy, C. N. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.20.2181 · Cited by 96 · see citing works
Class A Calcium Channel Variants in Pancreatic Islets and Their Role in Insulin Secretion
Ligon, B., BOYD, A. E., & Dunlap, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13905 · Cited by 91 · see citing works
CECCHETTI, G., Binda, A., Piperno, A., Nador, F., Fargion, S., & FIORELLI, G. (1991) · European Heart Journal · doi:10.1093/oxfordjournals.eurheartj.a059873 · Cited by 85 · see citing works
Winegar, B. D., Kelly, R., & Lansman, J. B. (1991) · The Journal of General Physiology · doi:10.1085/jgp.97.2.351 · Cited by 74 · see citing works
Mikus, G., Eichelbaum, M. F., Fischer, C., Gumułka, S. W., Klotz, U. E., & Kroemer, H. K. (1990) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)13200-x · Cited by 72 · see citing works
Jensen, C. E., Tuck, S. M., Old, J., Morris, R. W., Yardumian, A., Sanctis, V. D., Hoffbrand, A. V., & Wonke, B. (1997) · European Journal Of Haematology · doi:10.1111/j.1600-0609.1997.tb00729.x · Cited by 68 · see citing works
Rychkov, G. Y., Brereton, H. M., Harland, L. M., & Barritt, G. J. (2001) · Hepatology · doi:10.1053/jhep.2001.23051 · Cited by 64 · see citing works
Growth, Puberty and Endocrine Function in Beta-Thalassaemia Major
Low, L. C. K. (1997) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem.1997.10.2.175 · Cited by 61 · see citing works
Ca 2+ Signaling in Cardiac Myocytes Overexpressing the α 1 Subunit of L-Type Ca 2+ Channel
Song, L., Guia, A., Muth, J. N., Rubio, M., Wang, S., Xiao, R.-P., Josephson, I. R., Lakatta, E. G., Schwartz, A., & Cheng, H. (2002) · Circulation Research · doi:10.1161/hh0202.103230 · Cited by 61 · see citing works
Self-citationPalka, P., Macdonald, G. A., Lange, A., & Burstow, D. J. (2002) · Journal of the American Society of Echocardiography · doi:10.1067/mje.2002.118032 · Cited by 53 · see citing works
Carvalho, M. C., de Oliveira, C. H., Mendes, G. D., Sucupira, M. C. A., de Moraes, M. E. A., & Nucci, G. D. (2001) · Biopharmaceutics & Drug Disposition · doi:10.1002/bdd.282 · Cited by 50 · see citing works
Link, G., Konijn, A. M., & Hershko, C. (1999) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(99)90011-2 · Cited by 49 · see citing works
Hemochromatosis: The genetic disorder of the twenty–first century
Barton, J. C., & Bertoli, L. F. (1996) · Nature Medicine · doi:10.1038/nm0496-394 · Cited by 47 · see citing works
Hershko, C., Link, G., & Pinson, A. (1987) · PubMed · Cited by 47 · see citing works
Use of transgenic mice to study voltage-dependent Ca2+ channels
Muth, J. N., Váradi, G., & Schwartz, A. (2001) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01797-1 · Cited by 46 · see citing works
Self-citationCharacterization of Fe2+ and Fe3+ transport by iron-loaded cardiac myocytes
Parkes, J. G. (1997) · Toxicology · doi:10.1016/s0300-483x(96)03566-4 · Cited by 42 · see citing works
Gharzuddine, W. (2002) · European Journal of Echocardiography · doi:10.1053/euje.2001.0114 · Cited by 40 · see citing works
Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels
Nawrath, H., & Wegener, J. W. (1996) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/pl00004921 · Cited by 39 · see citing works
Chronopharmacology of intravenous and oral modified release verapamil
Dilger, K., Eckhardt, K., Hofmann, U., Kucher, K., Mikus, G., & Eichelbaum, M. (1999) · British Journal of Clinical Pharmacology · doi:10.1046/j.1365-2125.1999.00910.x · Cited by 27 · see citing works
Pharmacokinetics of verapamil in overdose
Kivistö, K. T., Neuvonen, P. J., & Tarssanen, L. T. (1997) · Human & Experimental Toxicology · doi:10.1177/0960327197016001071 · Cited by 21 · see citing works
Once a day verapamil in essential hypertension.
Müller, F. B., Ha, H., Hotz, H. W., Schmidlin, O., Folláth, F., & Fr, B. (1986) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.1986.tb02863.x · Cited by 21 · see citing works
Cellular electrophysiology of amlodipine: Probing the cardiac L-type calcium channel
Kass, R. S., Arena, J. P., & Chin, S. (1989) · The American Journal of Cardiology · doi:10.1016/0002-9149(89)90958-2 · Cited by 21 · see citing works
Galanello, R. (2001) · Seminars in Hematology · doi:10.1016/s0037-1963(01)90063-0 · Cited by 18 · see citing works
Cardiac abnormalities in hemochromatosis
Muhlestein, J. B. (2000) · Cambridge University Press eBooks · doi:10.1017/cbo9780511666476.029 · Cited by 18 · see citing works
Diabetes mellitus and hemochromatosis
Strohmeyer, G. W., & Niederau, C. (2000) · Cambridge University Press eBooks · doi:10.1017/cbo9780511666476.026 · Cited by 11 · see citing works
Regulation of L-type Calcium Channels in Pituitary GH4C1 Cells by Depolarization
Peri, R., Triggle, D. J., & Singh, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102613200 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Two to tango: Regulation of Mammalian iron metabolism
Hentze, M. W., Muckenthaler, M. U., Galy, B., & Camaschella, C. (2010) · Cell · doi:10.1016/j.cell.2010.06.028 · Cited by 2,120 · see citing works
Hentze, M. W., Muckenthaler, M. U., & Andrews, N. C. (2004) · Cell · doi:10.1016/s0092-8674(04)00343-5 · Cited by 1,736 · see citing works
Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
“The clinical severity of hemochromatosis is related to NTBI, a toxic iron species bound to low molecular weight molecules, easily taken up by hepatocytes and pancreatic cells via ZIP14 transporter(82) and by cardiomyocytes through other transporters.(83) While iron uptake by transferrin receptor is tightly regulated,…”
Non-transferrin bound iron: a key role in iron overload and iron toxicity
Brissot, P., Ropert, M., Le Lan, C., & Loréal, O. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.07.014 · Cited by 654 · see citing works
Andrews, N. C., & Schmidt, P. J. (2006) · Annual Review of Physiology · doi:10.1146/annurev.physiol.69.031905.164337 · Cited by 640 · see citing works
Forging a field: the golden age of iron biology.
Andrews, N. C. (2008) · Blood · doi:10.1182/blood-2007-12-077388 · Cited by 623 · see citing works
Mechanisms of mammalian iron homeostasis
Pantopoulos, K., Porwal, S. K., Tartakoff, A., & Devireddy, L. (2012) · Biochemistry · doi:10.1021/bi300752r · Cited by 598 · see citing works
Regulation of iron transport and the role of transferrin
Gkouvatsos, K., Papanikolaou, G., & Pantopoulos, K. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2011.10.013 · Cited by 518 · see citing works
The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease
Oudit, G. Y. (2004) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2004.05.015 · Cited by 467 · see citing works
Self-citationRegulation of iron acquisition and storage: consequences for iron-linked disorders
De Domenico, I., McVey Ward, D., & Kaplan, J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2295 · Cited by 464 · see citing works
Brissot, P., Pietrangelo, A., Adams, P. C., de Graaff, B., McLaren, C. E., & Loréal, O. (2018) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2018.16 · Cited by 430 · see citing works
Gunshin, H., Fujiwara, Y., Custodio, A. O., DiRenzo, C., Robine, S., & Andrews, N. C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24356 · Cited by 419 · see citing works
Chen, P., Wu, Q., Feng, J., Yan, L., Sun, Y., Liu, S., Yu, X., Zhang, M., Pan, T. S., Chen, X., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-0149-3 · Cited by 413 · see citing works
Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure
Nakayama, H., Chen, X., Baines, C. P., Klevitsky, R., Zhang, X., Zhang, H., Jaleel, N., Chua, B. H. L., Hewett, T. E., Robbins, J. M., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31060 · Cited by 405 · see citing works
Cardiovascular Function and Treatment in β-Thalassemia Major
Pennell, D. J., Udelson, J. E., Arai, A. E., Bozkurt, B., Cohen, A. R., Galanello, R., Hoffman, T. M., Kiernan, M. S., Lerakis, S., Piga, A. G., et al. (2013) · Circulation · doi:10.1161/cir.0b013e31829b2be6 · Cited by 394 · see citing works
Seferovic, P. M., Polovina, M. M., Bauersachs, J. K., Arad, M., Gal, T. B., Lund, L. H., Felix, S. B., Arbustini, E., Caforio, A. L. P., Farmakis, D. T., et al. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1461 · Cited by 391 · see citing works
Iron Overload Cardiomyopathy in Clinical Practice
Kremastinos, D. T., & Farmakis, D. T. (2011) · Circulation · doi:10.1161/circulationaha.111.050773 · Cited by 358 · see citing works
Gujja, P., Rosing, D. R., Tripodi, D. J., & Shizukuda, Y. (2010) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2010.03.083 · Cited by 328 · see citing works
Iron metabolism in the anemia of chronic disease
Weiss, G. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2008.08.006 · Cited by 322 · see citing works
Anderson, G. J., & Vulpe, C. D. (2009) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-009-0051-1 · Cited by 317 · see citing works
Iron-Overload Cardiomyopathy: Pathophysiology, Diagnosis, and Treatment
Murphy, C. J., & Oudit, G. Y. (2010) · Journal of Cardiac Failure · doi:10.1016/j.cardfail.2010.05.009 · Cited by 307 · see citing works
Self-citationMechanisms of Brain Iron Transport: Insight into Neurodegeneration and CNS Disorders
Mills, E., Dong, X.-P., Wang, F., & Xu, H. (2010) · Future Medicinal Chemistry · doi:10.4155/fmc.09.140 · Cited by 309 · see citing works
Evstatiev, R., & Gasché, C. (2011) · Gut · doi:10.1136/gut.2010.214312 · Cited by 292 · see citing works
LPI-labile plasma iron in iron overload
Cabantchik, Z. I., BREUER, W., Zanninelli, G., & Cianciulli, P. (2005) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2004.10.003 · Cited by 291 · see citing works
Eid, R., Arab, N. T. T., & Greenwood, M. T. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2016.12.002 · Cited by 286 · see citing works
Oudit, G. Y., Kassiri, Z., PATEL, M., Chappell, M. C., BUTANY, J. W., Backx, P. H., Tsushima, R. G., Scholey, J. W., Khokha, R., & Penninger, J. M. (2007) · Cardiovascular Research · doi:10.1016/j.cardiores.2007.04.007 · Cited by 247 · see citing works
Self-citationCellular transport and homeostasis of essential and nonessential metals
Martinez‐Finley, E. J., Chakraborty, S., Fretham, S. J. B., & Aschner, M. (2012) · Metallomics · doi:10.1039/c2mt00185c · Cited by 239 · see citing works
Magnetic resonance imaging measurement of iron overload
Wood, J. C. (2007) · Current Opinion in Hematology · doi:10.1097/moh.0b013e3280d2b76b · Cited by 241 · see citing works
Guidelines for evaluating myocardial cell death
Mishra, P. K., Adameová, A., Hill, J. A., Baines, C. P., Kang, P. M., Downey, J. M., Narula, J., Takahashi, M., Abbate, A., Piristine, H. C., et al. (2019) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00259.2019 · Cited by 238 · see citing works
Tanner, M. A., Galanello, R., Dessì, C., Smith, G. C., Westwood, M. A., Agus, A., Pibiri, M., Nair, S. V., Walker, J. M., & Pennell, D. J. (2008) · Journal of Cardiovascular Magnetic Resonance · doi:10.1186/1532-429x-10-12 · Cited by 237 · see citing works
Oudit, G. Y., Herzenberg, A. M., Kassiri, Z., Wong, D., Reich, H. N., Khokha, R., Crackower, M. A., Backx, P. H., Penninger, J. M., & Scholey, J. W. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.051091 · Cited by 231 · see citing works
Self-citationOudit, G. Y., Trivieri, M. G., Khaper, N., Husain, T., Wilson, G. J., Liu, P., Sole, M. J., & Backx, P. H. (2004) · Circulation · doi:10.1161/01.cir.0000124229.40424.80 · Cited by 224 · see citing works
Self-citationRole of L-type Ca2+ channels in iron transport and iron-overload cardiomyopathy
Oudit, G. Y., Trivieri, M. G., Khaper, N., Liu, P. P., & Backx, P. H. (2006) · Journal of Molecular Medicine · doi:10.1007/s00109-005-0029-x · Cited by 222 · see citing works
Self-citationNon-transferrin-bound iron transporters
Knutson, M. D. (2019) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.413 · Cited by 221 · see citing works
Longitudinal analysis of heart and liver iron in thalassemia major
Noetzli, L. J., Carson, S., Nørd, A., Coates, T. D., & Wood, J. C. (2008) · Blood · doi:10.1182/blood-2008-04-148767 · Cited by 220 · see citing works
Anderson, E. R., & Shah, Y. M. (2012) · Comprehensive physiology · doi:10.1002/cphy.c120016 · Cited by 249 · see citing works
Joza, N. A., Oudit, G. Y., Brown, D., Bénit, P., Kassiri, Z., Vahsen, N., Benoît, L. A., Patel, M. M., Nowikovsky, K., Vassault, A. J., et al. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10261-10272.2005 · Cited by 206 · see citing works
Self-citationEfficacy of deferasirox in reducing and preventing cardiac iron overload in β-thalassemia
Pennell, D. J., Porter, J. B., Cappellini, M. D., El-Beshlawy, A. M., Chan, L. L., Aydınok, Y., Elalfy, M. S., Sutcharitchan, P., Li, C. K., Ibrahim, H. M., et al. (2009) · Blood · doi:10.1182/blood-2009-04-217455 · Cited by 194 · see citing works
Iron homeostasis: An anthropocentric perspective
Coffey, R., & Ganz, T. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.781823 · Cited by 189 · see citing works
Physiology and pathophysiology of iron in hemoglobin-associated diseases
Coates, T. D. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.039 · Cited by 181 · see citing works
Role of iron metabolism in heart failure: From iron deficiency to iron overload
Zhang, H., Zhabyeyev, P., Wang, S., & Oudit, G. Y. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.08.030 · Cited by 185 · see citing works
Self-citationBrain Iron Metabolism Dysfunction in Parkinson’s Disease
Jiang, H. F., Wang, J., Rogers, J. T., & Xie, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9879-1 · Cited by 183 · see citing works
Pathophysiology and Clinical Manifestations of the -ThalassemiasPreprint
Nienhuis, A. W., & Nathan, D. G. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011726 · Cited by 180 · see citing works
Graham, R. M. (2007) · World Journal of Gastroenterology · doi:10.3748/wjg.v13.i35.4725 · Cited by 180 · see citing works
Pathogenesis and management of iron toxicity in thalassemia
Hershko, C. (2010) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05544.x · Cited by 176 · see citing works
Restrictive cardiomyopathy: definition and diagnosis
Rapezzi, C., Aimo, A., Barison, A., Emdin, M., Porcari, A., Linhart, A., Keren, A., Merlo, M., & Sinagra, G. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehac543 · Cited by 174 · see citing works
Merle, U., Fein, E., Gehrke, S. G., Stremmel, W., & Kulaksiz, H. (2007) · Endocrinology · doi:10.1210/en.2006-1331 · Cited by 173 · see citing works
Oxidative stress in β-thalassaemia and sickle cell disease
Voskou, S., Aslan, M., Fanis, P., Phylactides, M., & Kleanthous, M. (2015) · Redox Biology · doi:10.1016/j.redox.2015.07.018 · Cited by 172 · see citing works
The Regulation of Cellular Iron Metabolism
Chua, A. C. G., Graham, R. M., Trinder, D., & Olynyk, J. K. (2007) · Critical Reviews in Clinical Laboratory Sciences · doi:10.1080/10408360701428257 · Cited by 168 · see citing works
Kassiri, Z., Oudit, G. Y., Sanchez, O. H., Dawood, F., Mohammed, F. F., Nuttall, R. K., Edwards, D. R., Liu, P. P., Backx, P. H., & Khokha, R. (2005) · Circulation Research · doi:10.1161/01.res.0000178789.16929.cf · Cited by 165 · see citing works
Self-citationThe Molecular Mechanisms of Iron Metabolism and Its Role in Cardiac Dysfunction and Cardioprotection
Ravíngerová, T., Kindernay, L., Barteková, M., Ferko, M., Adameová, A., Zohdi, V., Bernátová, I., Ferenczyová, K., & Lazou, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217889 · Cited by 165 · see citing works
Nature of non-transferrin-bound iron: studies on iron citrate complexes and thalassemic sera
Evans, R. W., Rafique, R., Zarea, A., Rapisarda, C., Cammack, R., Evans, P., Porter, J. B., & Hider, R. C. (2007) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-007-0297-8 · Cited by 164 · see citing works
Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal transporter-1
Ludwiczek, S., Theurl, I., Muckenthaler, M. U., Jakab, M., Mair, S. M., Theurl, M., Kiss, J., Paulmichl, M., Hentze, M. W., Ritter, M., et al. (2007) · Nature Medicine · doi:10.1038/nm1542 · Cited by 160 · see citing works
Basu, R., Oudit, G. Y., Wang, X., Zhang, L., Ussher, J. R., Lopaschuk, G. D., & Kassiri, Z. (2009) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00452.2009 · Cited by 161 · see citing works
Self-citationIron Metabolism in Cardiovascular Disease: Physiology, Mechanisms, and Therapeutic Targets
Sawicki, K. T., Jesus, A. D., & Ardehali, H. (2023) · Circulation Research · doi:10.1161/circresaha.122.321667 · Cited by 165 · see citing works
Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms
Gammella, E., Recalcati, S., Rybińska, I., Buratti, P., & Cairo, G. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2015/230182 · Cited by 157 · see citing works
Kattamis, A., Papassotiriou, I., Palaiologou, D., Apostolakou, F., Galani, A., Ladis, V., Sakellaropoulos, N., & Papanikolaou, G. (2006) · PubMed · Cited by 156 · see citing works
Ferrari, E., Palma, C., Vesentini, S., Occhetta, P., & Rasponi, M. (2020) · Biosensors · doi:10.3390/bios10090110 · Cited by 155 · see citing works
Inherited iron overload disorders
Piperno, A., Pelucchi, S., & Mariani, R. (2020) · Translational Gastroenterology and Hepatology · doi:10.21037/tgh.2019.11.15 · Cited by 151 · see citing works
Cardiac Involvement in Hemochromatosis
Gulati, V., Harikrishnan, P., Palaniswamy, C., Aronow, W. S., Jain, D., & Frishman, W. H. (2013) · Cardiology in Review · doi:10.1097/crd.0b013e3182a67805 · Cited by 147 · see citing works
Physiology and Pathophysiology of Iron Cardiomyopathy in Thalassemia
Wood, J. C., Enriquez, C. M., Ghugre, N. R., Otto‐Duessel, M., Aguilar, M. I., Nelson, M. D., Moats, R. A., & Coates, T. D. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1345.047 · Cited by 145 · see citing works
Iron overload: Effects on cellular biochemistry
Nogueira, L. S., Oliveira, M. M., Pessoa, M. T., & Barbosa, L. A. (2019) · Clinica Chimica Acta · doi:10.1016/j.cca.2019.11.029 · Cited by 144 · see citing works
Guidelines for quantifying iron overload
Wood, J. C. (2014) · Hematology · doi:10.1182/asheducation-2014.1.210 · Cited by 140 · see citing works
Regulated cell death pathways in cardiomyopathy
Sheng, S., Li, J., Hu, X., & Wang, Y. (2023) · Acta Pharmacologica Sinica · doi:10.1038/s41401-023-01068-9 · Cited by 131 · see citing works
Acute exposure to ZnO nanoparticles induces autophagic immune cell death
Johnson, B. M., Fraietta, J. A., Gracias, D. T., Hope, J. L., Stairiker, C. J., Patel, P. R., Mueller, Y. M., McHugh, M. D., Delaney, L. J., Wheatley, M. A., et al. (2014) · Nanotoxicology · doi:10.3109/17435390.2014.974709 · Cited by 128 · see citing works
Sendamarai, A. K., Ohgami, R. S., Fleming, M. D., & Lawrence, C. M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0801318105 · Cited by 130 · see citing works
Herceptin induces ferroptosis and mitochondrial dysfunction in H9c2 cells
Sun, L., Wang, H., Yu, S., Zhang, L., Jiang, J., & Zhou, Q. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.5072 · Cited by 125 · see citing works
Lekawanvijit, S., & Chattipakorn, N. (2009) · Canadian Journal of Cardiology · doi:10.1016/s0828-282x(09)70064-9 · Cited by 120 · see citing works
Oudit, G. Y., Kassiri, Z., Zhou, J., Liu, Q. C., Liu, P. P., Backx, P. H., Dawood, F., Crackower, M. A., Scholey, J. W., & Penninger, J. M. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn041 · Cited by 119 · see citing works
Self-citationDas, S. K., Wang, W., Zhabyeyev, P., Basu, R., McLean, B. A., Dong, F., Parajuli, N., DesAulniers, J., Patel, V. B., Hajjar, R. J., et al. (2015) · Scientific Reports · doi:10.1038/srep18132 · Cited by 115 · see citing works
Self-citationPelizzoni, I., Macco, R., Morini, M. F., Zacchetti, D., Grohovaz, F., & Codazzi, F. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00652.x · Cited by 110 · see citing works
Pelizzoni, I., Zacchetti, D., Campanella, A., Grohovaz, F., & Codazzi, F. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2013.04.007 · Cited by 111 · see citing works
Permeation, regulation and control of expression of TRP channels by trace metal ions
Bouron, A., Kiselyov, K. I., & Oberwinkler, J. (2014) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-014-1590-3 · Cited by 110 · see citing works
T‐type calcium channel blockade improves survival and cardiovascular function in thalassemic mice
Kumfu, S., Chattipakorn, S. C., Chinda, K., Fucharoen, S., & Chattipakorn, N. (2012) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2012.01779.x · Cited by 108 · see citing works
Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis
Wang, S., He, X.-Y., Wu, Q., Jiang, L., Chen, L., Yu, Y., Zhang, P., Huang, X., Wang, J., Ju, Z., et al. (2019) · Haematologica · doi:10.3324/haematol.2019.224899 · Cited by 99 · see citing works
Reardon, T. F., & Allen, D. G. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2008.046045 · Cited by 108 · see citing works
Cellular and mitochondrial iron homeostasis in vertebrates
Chen, C., & Paw, B. H. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2012.01.003 · Cited by 106 · see citing works
A T2* magnetic resonance imaging study of pancreatic iron overload in thalassemia major
Au, W. Y., Lam, W. W. M., Chu, C. W., Tam, S., Wong, W.-K., Liang, R. H. S., & Ha, S. (2007) · Haematologica · doi:10.3324/haematol.11768 · Cited by 106 · see citing works
Dual Role of ROS as Signal and Stress Agents: Iron Tips the Balance in favor of Toxic Effects
Gammella, E., Recalcati, S., & Cairo, G. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/8629024 · Cited by 106 · see citing works
Molecular control of iron metabolism
Andrews, N. C. (2005) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2004.10.004 · Cited by 107 · see citing works
The Pathophysiology of Transfusional Iron Overload
Porter, J. B., & Garbowski, M. (2014) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2014.04.003 · Cited by 120 · see citing works
Molecular and cellular bases of iron metabolism in humans
Васильевич, М. И., Suhodolo, I. V., Prokopieva, V. D., & Klimenteva, T. K. (2016) · Biochemistry (Moscow) · doi:10.1134/s0006297916060018 · Cited by 100 · see citing works
Concepts and goals in the management of transfusional iron overload
Porter, J. B. (2007) · American Journal of Hematology · doi:10.1002/ajh.21100 · Cited by 100 · see citing works
Garrick, M. D., & Garrick, L. M. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.03.018 · Cited by 102 · see citing works
Zhang, Z., Liu, D., Yi, B., Liao, Z., Tang, L., Yin, D., & He, M. L. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2544 · Cited by 98 · see citing works
The Ins and Outs of Iron Homeostasis
Donovan, A., Roy, C. N., & Andrews, N. C. (2006) · Physiology · doi:10.1152/physiol.00052.2005 · Cited by 100 · see citing works
The mutual control of iron and erythropoiesis
Camaschella, C., Pagani, A., Nai, A., & Silvestri, L. (2016) · International Journal of Laboratory Hematology · doi:10.1111/ijlh.12505 · Cited by 97 · see citing works
H+-Coupled Divalent Metal-Ion Transporter-1
Shawki, A., Knight, P. B., Maliken, B. D., Niespodzany, E. J., & Mackenzie, B. (2012) · Current topics in membranes · doi:10.1016/b978-0-12-394316-3.00005-3 · Cited by 94 · see citing works
T-type calcium channel as a portal of iron uptake into cardiomyocytes of beta-thalassemic mice
Kumfu, S., Chattipakorn, S. C., Srichairatanakool, S., Settakorn, J., Fucharoen, S., & Chattipakorn, N. (2010) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2010.01549.x · Cited by 95 · see citing works
Canedo, A., Gonçalves, B. B., Brito, R. D. S., Vieira, L. G., Lima, E. C. D. O., & Rocha, T. L. (2020) · Chemosphere · doi:10.1016/j.chemosphere.2020.126792 · Cited by 94 · see citing works
Iron metabolism and the role of the iron-regulating hormone hepcidin in health and disease
Daher, R., Manceau, H., & Karim, Z. (2017) · La Presse Médicale · doi:10.1016/j.lpm.2017.10.006 · Cited by 91 · see citing works
Involvement of cytosolic and mitochondrial iron in iron overload cardiomyopathy: an update
Gordan, R., Wongjaikam, S., Gwathmey, J. K., Chattipakorn, N., Chattipakorn, S. C., & Xie, L. (2018) · Heart Failure Reviews · doi:10.1007/s10741-018-9700-5 · Cited by 92 · see citing works
Rose, R. A., Sellan, M. E., Simpson, J. A., Izaddoustdar, F., Cifelli, C., Panama, B. K., Davis, M., Zhao, D., Markhani, M., Murphy, G. G., et al. (2011) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.110.960401 · Cited by 88 · see citing works
Self-citationIron entry in neurons and astrocytes: a link with synaptic activity
Codazzi, F., Pelizzoni, I., Zacchetti, D., & Grohovaz, F. (2015) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2015.00018 · Cited by 83 · see citing works
Iron and the heart: A paradigm shift from systemic to cardiomyocyte abnormalities
Paterek, A., Mackiewicz, U., & Ma̧czewski, M. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.28820 · Cited by 85 · see citing works
Cardiac iron overload in sickle‐cell disease
Meloni, A., Puliyel, M. M., Pepe, A., Berdoukas, V., Coates, T. D., & Wood, J. C. (2014) · American Journal of Hematology · doi:10.1002/ajh.23721 · Cited by 83 · see citing works
Ferroptosis mechanisms and regulations in cardiovascular diseases in the past, present, and future
Fang, W., Xie, S., & Deng, W. (2024) · Cell Biology and Toxicology · doi:10.1007/s10565-024-09853-w · Cited by 78 · see citing works
Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle
Barrientos, T., Laothamatas, I., Koves, T. R., Soderblom, E. J., Bryan, M. R., Moseley, M. A., Muoio, D. M., & Andrews, N. C. (2015) · EBioMedicine · doi:10.1016/j.ebiom.2015.09.041 · Cited by 80 · see citing works
Porter, J. B., Rafique, R., Srichairatanakool, S., Davis, B. A., Shah, F., HAIR, T., & Evans, P. (2005) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1345.018 · Cited by 80 · see citing works
Iron Chelation in Thalassemia Major
Borgna‐Pignatti, C., & Marsella, M. (2015) · Clinical Therapeutics · doi:10.1016/j.clinthera.2015.10.001 · Cited by 77 · see citing works
- Authors
- Oudit, G. Y., Sun, H., Trivieri, M. G., Koch, S. E., Dawood, F., Ackerley, C., Yazdanpanah, M., Wilson, G. J., Schwartz, A., Liu, P. P., & Backx, P. H.
- Affiliations
- University of Toronto (CA)
- University of Cincinnati Medical Center (US)
- Hospital for Sick Children (CA)
- University Health Network (CA)
- Corresponding author
- Backx, Peter H
- Venue
- Nature Medicine
- Published
- 2003-08-24
- Volume
- 9
- Issue
- 9
- Pages
- 1187-1194
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2094765038
- Cited by
- 480
- References
- 65
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 21 · 2023: 23 · 2022: 20 · 2021: 24 · 2020: 19 · 2019: 26 · 2018: 22 · 2017: 21 · 2016: 33 · 2015: 25 · 2014: 19 · 2013: 29 · 2012: 25
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Pfizer
- National Institutes of Health
- Canadian Institutes of Health Research
- National Heart, Lung, and Blood Institute (T32HL007382, P01HL022619)
- Topics
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- iron overload cardiomyopathy, L-type voltage-dependent calcium channels, iron absorption, cardiomyocytes, divalent cation transport, oxidative stress, calcium channel blockers, amlodipine, verapamil, cardiac function, myocardial fibrosis, iron overload
- MeSH terms
- Animals, Biological Transport, Calcium Channel Blockers, Iron, Male, Mice, Inbred Strains, Cardiomyopathies, Myocardium, Verapamil, Calcium Channels, Survival Rate, Amlodipine, Oxidative Stress, Iron Overload, Myocytes, Cardiac, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
