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Perspectives on the Role and Relevance of Copper in Cardiac Disease

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Abstract

Cardiac hypertrophy as a result of dietary copper deficiency has been studied for 40 plus years and is the subject of this review. While connective tissue anomalies occur, a hallmark pathology is cardiac hypertrophy, increased mitochondrial biogenesis, with disruptive cristae, vacuolization of mitochondria, and deposition of lipid droplets. Electrocardiogram abnormalities have been demonstrated along with biochemical changes especially as it relates to the copper-containing enzyme cytochrome c oxidase. The master controller of mitochondrial biogenesis, PGC1-α expression and protein, along with other proteins and transcriptional factors that play a role are upregulated. Nitric oxide, vascular endothelial growth factor, and cytochrome c oxidase all may enhance the upregulation of mitochondrial biogenesis. Marginal copper intakes reveal similar pathologies in the absence of cardiac hypertrophy. Reversibility of the copper-deficient rat heart with a copper-replete diet has resulted in mixed results, depending on both the animal model used and temporal relationships. New information has revealed that copper supplementation may rescue cardiac hypertrophy induced by pressure overload.

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References

  1. Fox PL (2003) The copper-iron chronicles: the story of an intimate relationship. Biometals 30:766–768

    Google Scholar 

  2. McCarthy DM, May RJ, Maher M, Brennan MF (1978) Trace metal and essential fatty acid deficiency during total parenteral nutrition. Am J Dig Dis 23:1009–1016

    Article  CAS  PubMed  Google Scholar 

  3. Kien CL, Ganther HE (1983) Manifestations of chronic selenium deficiency in a child receiving total parenteral nutrition. Am J Clin Nutr 37:319–328

    CAS  PubMed  Google Scholar 

  4. Medeiros DM, Wildman REC (2015) Advanced human nutrition, 3rd edn. Jones and Bartlett, Burlington, MA

    Google Scholar 

  5. Shields GS, Coulson WF, Kimball DA, Carnes WH, Cartwright GE, Wintrobe MM (1962) Studies on copper metabolism. 32. Cardiovascular lesions in copper-deficient swine. Am J Pathol 41:603–621

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Kelly WA, Kesterson JW, Carlton WW (1974) Myocardial lesions in the offspring of female rats fed a copper deficient diet. Exp Mol Pathol 20:40–56

    Article  CAS  PubMed  Google Scholar 

  7. Dallman PR, Goodman JR (1970) Enlargement of mitochondrial compartment in iron and copper deficiency. Blood 35:496–505

    CAS  PubMed  Google Scholar 

  8. Goodman JR, Warshaw JB, Dallman PR (1970) Cardiac hypertrophy in rats with iron and copper deficiency: quantitative contribution of mitochondrial enlargement. Pediatr Res 4:244–256

    Article  CAS  PubMed  Google Scholar 

  9. Lear PM, Heller LJ, Prohaska JR (1996) Cardiac hypertrophy in copper-deficient rats is not attenuated by angiotensin II receptor antagonist L-158,809. Proc Soc Exp Biol Med 212:284–292

    Article  CAS  PubMed  Google Scholar 

  10. Medeiros DM, Bagby D, Ovecka G, McCormick RJ (1991) Myofibrillar, mitochondrial and valvular morphological alterations in cardiac hypertrophy among copper deficient rats. J Nutr 121:815–824

    CAS  PubMed  Google Scholar 

  11. Medeiros DM, Liao Z, Hamlin RJ (1991) Copper deficiency in a genetically hypertensive cardiomyopathic rat: electrocardiogram, functional and ultrastructural aspects. J Nutr 1991(121):1026–1034

    Google Scholar 

  12. Medeiros DM, Failla ML, Schoenemann HM, Ovecka GD (1991) Morphometric analysis of myocardium from copper-deficient pigs. Nutr Res 11:1439–1450

    Article  CAS  Google Scholar 

  13. Pyatskowit JW, Prohaska JR (2008) Copper deficient rats and mice both develop anemia but only rats have lower plasma and brain iron levels. Comp Biochem Physiol C Toxicol Parmacol 147:316–323

    Article  Google Scholar 

  14. Medeiros DM, Liao Z, Hamlin RL (1992) Electrocardiographic activity and cardiac function in copper-restricted rats. Proc Soc Exp Biol Med 200:78–84

    Article  CAS  PubMed  Google Scholar 

  15. Medeiros DM, Davidson J, Jenkins JE (1993) A unified perspective on copper deficiency and cardiomyopathy. Proc Soc Exp Biol Med 203:262–273

    Article  CAS  PubMed  Google Scholar 

  16. Medeiros DM, Beard JL (1998) Dietary iron deficiency results in cardiac eccentric hypertrophy in rats. Proc Soc Exp Biol Med 218:370–375

    Article  CAS  PubMed  Google Scholar 

  17. Wildman REC, Medeiros DM, Hamlin RL, Stills H, Jones DA, Bonagura JD (1996) Aspects of cardio-myopathy in copper-deficient pigs: electrocardiography, echocardiography and ultrastructural findings. Biol. Tr. El. Res. 55:55–70

    Article  CAS  Google Scholar 

  18. Wu BN, Medeiros DM, Lin KN, Thorne BM (1984) Long term effects of dietary copper deficiency and sodium intake on blood pressures and serum profiles of Long-Evans rats. Nutr Res 4:305–314

    Article  CAS  Google Scholar 

  19. Medeiros DM, Bono E. (2011) The Iron factor in bone development In Diet, Nutrients, and Bone, J.J.B. Anderson, S.C. Garner, P.J. Klemmer, Taylor & Francis, Boca Raton, FL, pp 203–212

  20. Dawson R, Milne G, Williams RB (1982) Changes in the collagen of rat heart in copper-deficiency-induced cardiac hypertrophy. Cardiovasc Res 16:559–565

    Article  CAS  PubMed  Google Scholar 

  21. Davidson J, Medeiros DM, Hamlin RL (1992) Cardiac ultrastructural and electrophysiological abnormalities in postweanling copper restricted and repleted rats in the absence of hypertrophy. J Nutr 122:1566–1575

    CAS  PubMed  Google Scholar 

  22. Behmoaras J, Slove S, Seve S, Vranckx R, Sommer O, Jacob MP (2008) Differential expression of lysyl oxidase LOX1 and LOX during growth and aging suggests specific roles in elastin and collagen fiber remodeling in rat aorta. Rejuvenation Res 11:883–889

    Article  CAS  PubMed  Google Scholar 

  23. Prohaska JT, Heller LJ (1982) Mechanical properties of the copper deficient rat heart. J Nutr 112:2142–2150

    CAS  PubMed  Google Scholar 

  24. Corea L, Bentivoglio M, Verdecchia P (1983) Echocardiographic left ventricular hypertrophy related to arterial pressure and plasma norepinephrine concentration in arterial hypertension. Rev Atenolol Treat Hypertens 5:837–843

    CAS  Google Scholar 

  25. Corea L, Bentivoglio M, Verdecchia P, Motolese M (1984) Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension. Am J Cardiol 53:1299–1303

    Article  CAS  PubMed  Google Scholar 

  26. Zimmer HG, Kilbeck-Ruhmkorff C, Zierhut W (1995) Cardiac hypertrophy induced by alpha and beta-adrenergic receptor stimulation. Cardioscience 6:47–57

    CAS  PubMed  Google Scholar 

  27. Kim BE, Turski ML, Nose Y, Casad M, Rockman HA, Thiele DJ (2010) Cardiac copper deficiency activates a systemic signaling mechanism that communicates with the copper acquisition and storage organs. Cell Metab 11:353–363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kaler SG (2011) ATP7A copper transport diseases: emerging concepts and future trends. Nat Rev Neurol 7:15–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Hicks JD, Donsante A, Pierson TM, Gillespie MJ, Chou DE, Kaler SG (2012) Increased frequency of congenital heart defects in Menkes disease. Clin Dysmorphol 21:59–63

    Article  PubMed  PubMed Central  Google Scholar 

  30. Prohaska JR (1983) Changes in tissue growth, concentrations of copper, iron, cytochrome c oxidase and super oxide dismutase subsequent to dietary or genetic copper deficiency in mice. J Nutr 113:2148–2158

    Google Scholar 

  31. Wildman REC, Medeiros DM, Jenkins J (1994) Comparative aspects of cardiac ultrastructure, morphometry and electrocardiography of hearts from rats fed restricted dietary copper and selenium. Biol Tr El Res 46:51–66

    Article  CAS  Google Scholar 

  32. Wildman REC, Medeiros DM, McCoy E (1995) Cardiac changes with dietary copper, iron or selenium restriction: organelle and basal laminae aberrations, decreased ventricular function and altered gross morphometry. J Tr El Exp Med 8:11–27

    CAS  Google Scholar 

  33. Cornblath M, Randle PJ, Parmeggiana A, Morgan HE (1963) Regulation of glycogenolysis in muscle: effects of glucagon and anoxia on lactate production, glycogen content, and phosphorylase activity in the perfused rat heart. J Biol Chem 238:1592–1597

    CAS  PubMed  Google Scholar 

  34. Liedtke AJ. (1981). Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog. Cardiovasc Dis 23:321–336

  35. Opie LH (1976) Effects of regional ischemia on metabolism of glucose and fatty acids: relative rates of aerobic and anaerobic energy production during myocardial infarction and comparison with the effects of anoxia. Circ Res 10:52–68

    Google Scholar 

  36. Bilheimer DW, Buja LM, Parkey RW, Bonte FJ, Wilkerson JT (1978) Fatty acid accumulation and abnormal lipid deposition in peripheral and border zones of experimental myocardial infarcts. J Nucl Med 19:276–283

    CAS  PubMed  Google Scholar 

  37. Burton KP, Templeton GH, Hagler HK, Willerson JT, Buja LM (1980) Effect of glucose availability on functional membrane integrity, ultrastructure, and contractile performance following hypoxia and reoxygenation in isolated feline cardiac muscle. J Mol Cardiol 12:109–133

    Article  CAS  Google Scholar 

  38. Burton KP, Buja LM, Sen A, Willerson JT, Chien KR (1986) Accumulation of arachidonate in triacylglycerols and unesterified fatty acids during ischemia and reflow in the isolated rat heart. Correlation with the loss of contractile function and the development of calcium overload. Am J Pathol 124:238–245

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Gong K, Jodalen H, Strangeland L, Vik-mo V, Lekven J (1986) Cellular lipid accumulation in different regions of myocardial infarcts in cats during beta adrenergic blockade with timolol. Cardiovasc Res 20:248–255

    Article  Google Scholar 

  40. Wildman REC, Hopkins R, Failla ML, Medeiros DM (1995) Marginal copper-restricted diets produce altered cardiac ultrastructure in the rat. Proc Soc Exp Biol 210:43–49

    Article  CAS  PubMed  Google Scholar 

  41. Viestenz KE, Klevay LM (1982) A randomized trial of copper therapy in rats with electrocardiographic abnormalities due to copper deficiency. Am J Clin Nutr 35:258–266

    CAS  PubMed  Google Scholar 

  42. Kopp SJ, Klevay LM, Feliksik JM (1983) Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. Am J Phys 245(5 Pt 1):H855–H866

    CAS  Google Scholar 

  43. Chao JCJ, Medeiros DM, Altschuld RA, Hohl CM (1993) Cardiac nucleotide levels and mitochondrial respiration in copper-deficient rats. Comp Biochem Physiol 104A:163–168

    Article  CAS  Google Scholar 

  44. Rusinko N, Prohaska JR (1985) Adenine nucleotide and lactate levels in organs from copper-deficient mice and brindled mice. J Nutr 115:936–943

    CAS  PubMed  Google Scholar 

  45. Liao Z, Allred J, Keen CL, McCune SA, Rucker RB, Medeiros DM (1995) Copper deficiency alters isomyosin types and levels of laminin, fibronectin and cytochrome c oxidase subunits from rat hearts. Comp Biochem Physiol 111B:61–67

    Article  CAS  Google Scholar 

  46. Liao Z, Medeiros DM, McCune SA, Prochaska LH (1995) Cardiac levels of fibronectin, laminin, isomyosins, and cytochrome c oxidase of weanling rats are more vulnerable to copper-deficiency than those of postweanling rats. J Nutr Biochem 6:385–391

    Article  CAS  PubMed  Google Scholar 

  47. Capaldi RA (1990) Structure and assembly of cytochrome c oxidase. Arch Biochem Biophys 280:252–262

    Article  CAS  PubMed  Google Scholar 

  48. Medeiros DM, Shiry L, Lincoln AJ, Prochaska L (1993) Cardiac non-myofibrillar proteins in copper-deficient rats: amino acid sequencing and western blotting of altered proteins. Biol Tr El Res 36:271–282

    Article  CAS  Google Scholar 

  49. Chao CJJ, Medeiros DM, Davidson J, Shiry L (1994) Decreased levels of ATP synthase and cytochrome c oxidase subunit peptide from hearts of copper-deficient rats are not altered by the administration of dimethyl sulfoxide. J Nutr 124:789–803

    CAS  PubMed  Google Scholar 

  50. Chen X, Jennings D, Medeiros DM (2005) Mitochondrial membrane potential is reduced in copper-deficient C2C12 cells in the absence of apoptosis. Biol Tr El Res 106:51–63

    Article  CAS  Google Scholar 

  51. Zeng H, Saari JT, Johnson WT (2007) Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart. J Nutr 137:14–18

    CAS  PubMed  Google Scholar 

  52. Johnson WT, Anderson CM (2008) Cardiac cytochrome C oxidase activity and contents of subunits 1 and 4 are altered in offspring by low prenatal copper intake by rat dams. J Nutr 138:1269–1273

    CAS  PubMed  Google Scholar 

  53. Getz J, Lin D, Medeiros DM (2001) The cardiac copper chaperone proteins Sco1 and CCS are up-regulated, but Cox1 and Cox4 are down-regulated, by copper deficiency. Biol. Trace El. Res. 143:368–377

    Article  Google Scholar 

  54. Medeiros DM, Shiry L, Samelman T (1997) Cardiac nuclear encoded cytochrome c oxidase subunits are decreased with copper restriction but not from iron restriction: gene expression, protein synthesis and heat shock protein aspects. Comp Biochem Physiol 117A:77–87

    Article  CAS  Google Scholar 

  55. Dong D, Xu X, Yin W, Kang YJ (2014) Changes in copper concentrations affect the protein levels but not the mRNA levels of copper chaperones in human umbilical vein endothelial cells. Metallomics 6:554–559

    Article  CAS  PubMed  Google Scholar 

  56. Prohaska JR, Gybina AA (2004) Intracellular copper transport in mammals. J Nutr 134:1003–1006

    CAS  PubMed  Google Scholar 

  57. Chao CJ. (1993) Studies on cardiac energy supply, mitochondrial respiration, ATP synthase and cytochrome c oxidase in copper-deficient and/or dimethyl sulfoxide-treated rats from biochemical ad molecular perspectives. Doctoral Dissertation, The Ohio State University

  58. Chen X, Jennings DB, Medeiros DM (2002) Impaired cardiac mitochondrial membrane potential and respiration in copper-deficient rats. J Bioenerg Biomem 34:397–406

    Article  CAS  Google Scholar 

  59. Klaahsen D, Ricklefs K, Medeiros DM (2007) Differential expression of genes involved with apoptosis, cell cycle, connective tissue proteins, fuel substrate utilization, inflammation, and mitochondrial biogenesis in copper-deficient rat hearts: implication of a role for Nfkb1. J Nutr Biochem 18:719–726

    Article  CAS  PubMed  Google Scholar 

  60. Medeiros DM, Jiang Y, Klaahsen D, Lin D (2009) Mitochondrial and sarcoplasmic protein changes in hearts from copper deficient rats: upregulation of PGC1-α transcript and protein as a cause for mitochondrial biogenesis in copper deficiency. J Nutr Biochem 20:823–830

    Article  CAS  PubMed  Google Scholar 

  61. Jin JK, Whittaker R, Glassy MS, Barlow SB, Gottlieb RA, Glembotski CC (2008) Localization of phosphorylated alpha B-crystallin to heart mitochondria during ischemia-reperfusion. Am J Physiol Heart Circ Physiol 294:H337–H344

    Article  CAS  PubMed  Google Scholar 

  62. Dohke T, Wada A, Isono T, Fujii M, Yamamoto T, Tsutamoto T, Horie M (2006) Proteomic analysis reveals significant alternations of cardiac small heat shock protein expression in congestive heart failure. J Card Fail 12:77–84

    Article  CAS  PubMed  Google Scholar 

  63. Keller A, Rouzeau JD, Farhadian F, Wisnewsky C, Marotte F, Lamandé N, Samuel JL, Schwartz K, Lazar M, Lucas M (1995) Differential expression of alpha- and beta-enolase genes during rat heart development and hypertrophy. Am J Phys 269(6 Pt 2):H1843–1851

    CAS  Google Scholar 

  64. Dzeja PP, Redfield MM, Burnett JC, Terzic A (2000) Failing energetics in failing hearts. Curr Cardiol Rep 2:212–217

    Article  CAS  PubMed  Google Scholar 

  65. Iwata K, Nishinaka T, Matsuno K, Kakehi T, Katsuyama M, Ibi M, Yabe-Nishimura C (2007) The activity of aldose reductase is elevated in diabetic mouse heart. J Pharmacol Sci 103:408–416

    Article  CAS  PubMed  Google Scholar 

  66. Singh N, Medeiros DM (1984) Liver fatty acid profiles and trace element concentrations in heart and liver of copper deficient rats. Biol Trace El Res 6:423–429

    Article  CAS  Google Scholar 

  67. Mao S, Leone TC, Kelly DP, Medeiros DM (2000) Mitochondrial transcription factor A is increased but expression of ATP synthase β subunit and medium-chain acyl-CoA dehydrogenase genes are decreased in hearts from copper-deficient rats. J Nutr 130:2143–2150

    CAS  PubMed  Google Scholar 

  68. Mao S, Medeiros DM (2001) Nuclear respiratory factors 1 and 2 are upregulated in hearts from copper-deficient rats. Biol Trace El Res 83:57–68

    Article  CAS  Google Scholar 

  69. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839

    Article  CAS  PubMed  Google Scholar 

  70. Duncan JG, Fong JL, Medeiros DM, Fink BM, Kelly DP (2007) Insulin-resistant heart exhibits a mitochondrial biogenic response driven by the peroxisome proliferator-activated receptor-α/PGC-1α gene regulatory pathway. Circulation 115:909–917

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Saari JT, Wold LE, Duan J, Ren J, Carlson HL, Bode AM, Lentsch AB, Zeng H, Schuschke DA (2007) Cardiac nitric oxide synthases are elevated in dietary copper deficiency. J Nutr Biochem 18:443–448

    Article  CAS  PubMed  Google Scholar 

  72. Nisoli E, Clementi E, Paolucci C, Cozzi V, Tonella C, Sciorata C, Bracale R, Valerio A, Francolini M, Moncada S, Carruba MO (2003) Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science 299:896–899

    Article  CAS  PubMed  Google Scholar 

  73. OuYang KX, Liang J, Yang Z-N, Zhao J-J (2015) A study on the inhibition of VEGF expression in salivary gland adenoid cystic carcinoma cells via iNOS gene RNAi in vitro. J Oral Pathol Med 44:153–158

    Article  CAS  Google Scholar 

  74. Arany Z, Fou S-Y, May Y, Ruas JL, Bommi-Reddy A, Girnum G, Cooper M, Laznik D, Chinsoboon J, Rangwala DM, Baek KH, Rosenzweig A, Spiegelman BM (2008) HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1alpha. Nature 451:1008–1012

    Article  CAS  PubMed  Google Scholar 

  75. Nisoli E, Carruba MO (2006) Nitric oxide and mitochondrial biogenesis. J Cell Sci 119:2855–2862

    Article  CAS  PubMed  Google Scholar 

  76. Iwabu M, Yamauchi T, Okada-Iwabu M, Sato K, Nakagawa T, Funata M, Yamaguchi M, Namiki S, Nakayama R, Tabata M, Ogata H, Kubota N, et al. (2010) Adiponectin and adipoR1 regulate PGC-1 alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature 464:1313–1319

    Article  CAS  PubMed  Google Scholar 

  77. Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puiserver P. (2005) Nutrient control of glucose homeostasis through a complex of PGC-1 [alpha] and SIRT1. Nature 434:113–118

  78. Li Y, Wang L, Schuschke DA, Zhou Z, Saari JT, Kang YJ (2005) Marginal dietary copper restriction induces cardiomyopathy in rats. J Nutr 135:2130–2136

    CAS  PubMed  Google Scholar 

  79. Medeiros DM, Shiry LJ, McCune SA (2005) Marginal copper intakes over a protracted time period in genetically and non-genetically susceptible heart disease rats disturbs electrocardiograms and enhances lipid deposition. Nutr Res 25:663–672

    Article  CAS  Google Scholar 

  80. Elsherif L, Jiang Y, Saari JT, Kang YJ (2004) Dietary copper restriction-induced changes in myocardial gene expression and the effect of copper repletion. Exp Biol Med 229:616–622

    CAS  Google Scholar 

  81. Elsherif L, Wang LP, Saari JT, Kang YJ (2004) Regression of dietary copper restriction-induced cardiomyopathy by copper repletion in mice. J Nutr 134:855–860

    CAS  PubMed  Google Scholar 

  82. Zuo X, Xie H, Dong D, Jiang N, Zhu H, Kang YJ (2010) Cytochrome c oxidase is essential for copper induced regression of cardiomyocyte hypertrophy. Cardiovasc Toxicol 10:208–214

    Article  CAS  PubMed  Google Scholar 

  83. Davidson J, Medeiros DM, Hamlin RL, Jenkins JE (1993) Sub-maximal, aerobic exercise training exacerbates the cardiomyopathy of postweanling copper-depleted rats. Biol Trace El Res 38:251–272

    Article  CAS  Google Scholar 

  84. Mao S, Medeiros DM, Hamlin RL (1999) Marginal copper and high fat diet produces alterations in electrocardiograms and cardiac ultrastructure in male rats. Nutrition 15:890–898

    Article  CAS  PubMed  Google Scholar 

  85. Zhou Y, Jiang Y, Kang YJ (2007) Copper inhibition of hydrogen peroxide-induced hypertrophy in embryonic rat cardiac H9c2 cells. Exp Biol Med 232:385–389

    CAS  Google Scholar 

  86. Jiang Y, Reynolds C, Xiao C, Feng W, Zhou Z, Rodriguez W, Tyagi SC, Eaton JW, Saari JT, Kang JY (2007) Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. J Exp Med 204:657–666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. McKeag NA, McKinley MC, Woodside JV, Harbinson MT, McKeown PP (2012) The role of micronutrients in heart failure. J Acad Nutr Diet 112:870–886

    Article  CAS  PubMed  Google Scholar 

  88. Klevay LM (2011) Is the western diet adequate in copper? J Trace Elem Med Biol 25:204–212

    Article  CAS  PubMed  Google Scholar 

  89. (2001) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. National Academy Press, Washington DC

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  1. Division of Biochemistry and Molecular Biology, School of Graduate Studies, University of Missouri Kansas City, 300F Administrative Center, 5115 Oak Street, Kansas City, MO, 64110-2499, USA

    Denis M. Medeiros

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Medeiros, D.M. Perspectives on the Role and Relevance of Copper in Cardiac Disease. Biol Trace Elem Res 176, 10–19 (2017). https://doi.org/10.1007/s12011-016-0807-z

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