Skip to main content

Advertisement

SpringerLink
Log in

Ischemia-induced Copper Loss and Suppression of Angiogenesis in the Pathogenesis of Myocardial Infarction

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

Myocardial ischemia is a primary cause for the loss of vital components such as cardiomyocytes in the heart, leading to myocardial infarction and eventual cardiac dysfunction or heart failure. Suppressed angiogenesis plays a determinant role in the pathogenesis of myocardial infarction. In response to myocardial ischemia, hypoxia-inducible factor-1α and 2α (HIF-1α and HIF-2α) accumulate in cardiomyocytes and other cell types. This would up-regulate the expression of genes involved in angiogenesis such as vascular endothelial growth factor (VEGF); however, it is often observed that the angiogenic capacity is suppressed rather than enhanced. Ischemic toxicity, which has not been fully recognized, is highly responsible for the compromised angiogenic capacity. One of the toxic effects resulting from myocardial ischemia is the loss of copper content in the heart. Although the reason for this loss has not been elucidated, the essential role of copper in the regulation of HIF-1 transcriptional activity has been described. Copper does not affect the accumulation of HIF-1α in the cell, but is required for the HIF-1 transcriptional complex formation and its interaction with the hypoxia-responsive element in target genes. Copper supplementation can stimulate the transcriptional activity of HIF-1 and restore angiogenic capacity, leading to increased capillary density in the heart. The recognition of ischemic toxicity and the effort to overcome the toxic effect would help develop alternative approaches in the treatment of ischemic heart disease.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ARNT:

Aryl hydrocarbon nuclear translocator

CCS:

Copper chaperon for Cu, Zn-superoxide dismutase

CFF:

Coronary flow fraction

FIH-1:

Factor inhibiting HIF-1 (hypoxia-inducible factor-1)

Glut-1:

Glucose transport-1

HER2:

Human epidermal growth factor receptor 2

HIF-1α:

Hypoxia-inducible factor-1α

HIF-2α:

Hypoxia-inducible factor-2α

HO-1:

Heme oxygenase-1

HRE:

Hypoxia-responsive element

IGF:

Insulin-like growth factor

iNOS:

Inducible nitric oxide synthase

PHDs:

Prolyl hydroxylase domain–containing proteins

PI3-kinases:

Phosphatidylinositol 3-kinases

pVHL:

Von Hippel–Lindau protein

TEPA:

Tetraethylenepentamine

VEGF:

Vascular endothelial growth factor

References

  1. Goswami, S. K., & Das, D. K. (2010). Oxygen sensing, cardiac ischemia, HIF-1alpha and some emerging concepts. Current Cardiology Reviews, 6, 265–273.

    Article  PubMed  CAS  Google Scholar 

  2. Tekin, D., Dursun, A. D., & Xi, L. (2010). Hypoxia inducible factor 1 (HIF-1) and cardioprotection. Acta Pharmacologica Sinica, 31, 1085–1094.

    Article  PubMed  CAS  Google Scholar 

  3. Eckle, T., Kohler, D., Lehmann, R., El Kasmi, K., & Eltzschig, H. K. (2008). Hypoxia-inducible factor-1 is central to cardioprotection: A new paradigm for ischemic preconditioning. Circulation, 118, 166–175.

    Article  PubMed  CAS  Google Scholar 

  4. Bautista, L., Castro, M. J., López-Barneo, J., & Castellano, A. (2009). Hypoxia inducible factor-2alpha stabilization and maxi-K+ channel beta1-subunit gene repression by hypoxia in cardiac myocytes: Role in preconditioning. Circulation Research, 104, 1364–1372.

    Article  PubMed  CAS  Google Scholar 

  5. Arab, A., Kuemmerer, K., Wang, J., Bode, C., & Hehrlein, C. (2008). Oxygenated perfluorochemicals improve cell survival during reoxygenation by pacifying mitochondrial activity. Journal of Pharmacology and Experimental Therapeutics, 325, 417–424.

    Article  PubMed  CAS  Google Scholar 

  6. Jürgensen, J. S., Rosenberger, C., Wiesener, M. S., Warnecke, C., Hörstrup, J. H., Gräfe, M., et al. (2004). Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium. The FASEB Journal, 18, 1415–1417.

    Google Scholar 

  7. Meeson, A. P., Radford, N., Shelton, J. M., Mammen, P. P., DiMaio, J. M., Hutcheson, K., et al. (2001). Adaptive mechanisms that preserve cardiac function in mice without myoglobin. Circulation Research, 88, 713–720.

    Article  PubMed  CAS  Google Scholar 

  8. Shohet, R. V., & Garcia, J. A. (2007). Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia. Journal of Molecular Medicine (Berlin, Germany), 85, 1309–1315.

    Article  Google Scholar 

  9. Kim, J. W., Tchernyshyov, I., Semenza, G. L., & Dang, C. V. (2006). HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell Metabolism, 3, 177–185.

    Article  PubMed  Google Scholar 

  10. Rey, S., & Semenza, G. L. (2010). Hypoxia-inducible factor-1-dependent mechanisms of vascularization and vascular remodelling. Cardiovascular Research, 86, 236–242.

    Article  PubMed  CAS  Google Scholar 

  11. Hinkel, R., Trenkwalder, T., & Kupatt, C. (2011). Gene therapy for ischemic heart disease. Expert Opinion on Biological Therapy, 11, 723–737.

    Article  PubMed  CAS  Google Scholar 

  12. Tyagi, S. C. (1997). Vasculogenesis and angiogenesis: Extracellular matrix remodeling in coronary collateral arteries and the ischemic heart. Journal of Cellular Biochemistry, 65, 388–394.

    Article  PubMed  CAS  Google Scholar 

  13. Metivier, F., Marchais, S. J., Guerin, A. P., Pannier, B., & London, G. M. (2000). Pathophysiology of anaemia: Focus on the heart and blood vessels. Nephrology, Dialysis, Transplantation, 15(Suppl 3), 14–18.

    Article  PubMed  Google Scholar 

  14. Frangogiannis, N. G., & Entman, M. L. (2005). Chemokines in myocardial ischemia. Trends in Cardiovascular Medicine, 15, 163–169.

    Article  PubMed  CAS  Google Scholar 

  15. Chevion, M., Jiang, Y., Har-El, R., Berenshtein, E., Uretzky, G., & Kitrossky, N. (1993). Copper and iron are mobilized following myocardial ischemia: Possible predictive criteria for tissue injury. Proceedings of the National Academy of Sciences of the United States of America, 90, 1102–1106.

    Article  PubMed  CAS  Google Scholar 

  16. Tapiero, H., Townsend, D. M., & Tew, K. D. (2003). Trace elements in human physiology and pathology. Copper. Biomedicine & Pharmacotherapy, 57, 386–398.

    Article  CAS  Google Scholar 

  17. Davis, G. K., & Mertz, W. (1987). Trace elements in human and animal nutrition (pp. 301–364). New York: Academic Press.

    Google Scholar 

  18. Dutt, B., & Mills, C. F. (1960). Reproductive failure in rats due to copper deficiency. Journal of Comparative Pathology, 70, 120–125.

    PubMed  CAS  Google Scholar 

  19. Fell, B. F., Farquharson, C., & Riddoch, G. I. (1987). Kidney lesions in copper-deficient rats. Journal of Comparative Pathology, 97, 187–196.

    Article  PubMed  CAS  Google Scholar 

  20. Goodman, J. R., Warshaw, J. B., & Dallman, P. R. (1970). Cardiac hypertrophy in rats with iron and copper deficiency: Quantitative contribution of mitochondrial enlargement. Pediatric Research, 4, 244–256.

    Article  PubMed  CAS  Google Scholar 

  21. Kopp, S. J., Klevay, L. M., & Feliksik, J. M. (1983). Physiological and metabolic characterization of a cardiomyopathy induced by chronic copper deficiency. The American Journal of Physiology, 245, H855–H866.

    PubMed  CAS  Google Scholar 

  22. Elsherif, L., Ortines, R. V., Saari, J. T., & Kang, Y. J. (2003). Congestive heart failure in copper-deficient mice. Experimental Biology and Medicine (Maywood, NJ), 228, 811–817.

    CAS  Google Scholar 

  23. Wildman, R. E., Hopkins, R., Failla, M. L., & Medeiros, D. M. (1995). Marginal copper-restricted diets produce altered cardiac ultrastructure in the rat. Proceedings of the Society for Experimental Biology and Medicine, 210, 43–49.

    PubMed  CAS  Google Scholar 

  24. Li, Y., Wang, L., Schuschke, D. A., Zhou, Z., Saari, J. T., & Kang, Y. J. (2005). Marginal dietary copper restriction induces cardiomyopathy in rats. The Journal of Nutrition, 135, 2130–2136.

    PubMed  CAS  Google Scholar 

  25. Wester, P. O. (1965). Trace elements in human myocardial infarction determined by neutron activation analysis. Acta Medica Scandinavica, 178, 765–788.

    Article  PubMed  CAS  Google Scholar 

  26. Zama, N., & Towns, R. (1986). Cardiac copper, magnesium, and zinc in recent and old myocardial infarction. Biological Trace Element Research, 10, 201–208.

    Article  CAS  Google Scholar 

  27. Chipperfield, B., & Chipperfield, J. R. (1978). Differences in metal content of the heart muscle in death from ischemic heart disease. American Heart Journal, 95, 732–737.

    Article  PubMed  CAS  Google Scholar 

  28. Prohaska, J. R. (1990). Biochemical changes in copper deficiency. The American Journal of Clinical Nutrition, 1, 452–461.

    CAS  Google Scholar 

  29. Medeiros, D. M., Davidson, J., & Jenkins, J. E. (1993). A unified perspective on copper deficiency and cardiomyopathy. Proceedings of the Society for Experimental Biology and Medicine, 203, 262–273.

    PubMed  CAS  Google Scholar 

  30. Feng, W., Ye, F., Xue, W., Zhou, Z., & Kang, Y. J. (2009). Copper regulation of hypoxia-inducible factor-1 activity. Molecular Pharmacology, 75, 174–182.

    Article  PubMed  CAS  Google Scholar 

  31. Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995). Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proceedings of the National Academy of Sciences of the United States of America, 92, 5510–5514.

    Article  PubMed  CAS  Google Scholar 

  32. Huang, L. E., Gu, J., Schau, M., & Bunn, H. F. (1998). Regulation of hypoxia-inducible factor 1alpha is mediated by an O2-dependent degradation domain via the ubiquitin-proteasome pathway. Proceedings of the National Academy of Sciences of the United States of America, 95, 7987–7992.

    Article  PubMed  CAS  Google Scholar 

  33. Wang, G. L., & Semenza, G. L. (1993). General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proceedings of the National Academy of Sciences of the United States of America, 90, 4304–4308.

    Article  PubMed  CAS  Google Scholar 

  34. Jaakkola, P., Mole, D. R., Tian, Y. M., Wilson, M. I., Gielbert, J., Gaskell, S. J., et al. (2001). Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292, 468–472.

    Article  PubMed  CAS  Google Scholar 

  35. Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., et al. (2001). HIFalpha targeted for VHL-mediated destruction by proline hydroxylation: Implications for O2 sensing. Science, 292, 464–468.

    Article  PubMed  CAS  Google Scholar 

  36. Maxwell, P. H., Wiesener, M. S., Chang, G. W., Clifford, S. C., Vaux, E. C., Cockman, M. E., et al. (1999). The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature, 399, 271–275.

    Article  PubMed  CAS  Google Scholar 

  37. Masson, N., Willam, C., Maxwell, P. H., Pugh, C. W., & Ratcliffe, P. J. (2001). Independent function of two destruction domains in hypoxia-inducible factor-alpha chains activated by prolyl hydroxylation. The EMBO Journal, 20, 5197–5206.

    Article  PubMed  CAS  Google Scholar 

  38. Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T. Y., Huang, L. E., et al. (2000). Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nature Cell Biology, 2, 423–427.

    Article  PubMed  CAS  Google Scholar 

  39. Tanimoto, K., Makino, Y., Pereira, T., & Poellinger, L. (2000). Mechanism of regulation of the hypoxia-inducible factor-1 alpha by the von Hippel-Lindau tumor suppressor protein. The EMBO Journal, 19, 4298–4309.

    Article  PubMed  CAS  Google Scholar 

  40. Hirsila, M., Koivunen, P., Xu, L., Seeley, T., Kivirikko, K. I., & Myllyharju, J. (2005). Effect of desferrioxamine and metals on the hydroxylases in the oxygen sensing pathway. FASEB Journal, 19, 1308–1310.

    PubMed  CAS  Google Scholar 

  41. Ke, Q., Kluz, T., & Costa, M. (2005). Down-regulation of the expression of the FIH-1 and ARD-1 genes at the transcriptional level by nickel and cobalt in the human lung adenocarcinoma A549 cell line. International Journal of Environmental Research and Public Health, 2, 10–13.

    Article  PubMed  CAS  Google Scholar 

  42. Maxwell, P., & Salnikow, K. (2004). HIF-1: an oxygen and metal responsive transcription factor. Cancer Biology & Therapy, 3, 29–35.

    Article  CAS  Google Scholar 

  43. Yuan, Y., Hilliard, G., Ferguson, T., & Millhorn, D. E. (2003). Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. The Journal of Biological Chemistry, 278, 15911–15916.

    Article  PubMed  CAS  Google Scholar 

  44. Mahon, P. C., Hirota, K., & Semenza, G. L. (2001). FIH-1: A novel protein that interacts with HIF-1alpha and VHL to mediate repression of HIF-1 transcriptional activity. Genes & Development, 15, 2675–2686.

    Article  CAS  Google Scholar 

  45. Lando, D., Peet, D. J., Gorman, J. J., Whelan, D. A., Whitelaw, M. L., & Bruick, R. K. (2002). FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes & Development, 16, 1466–1471.

    Article  CAS  Google Scholar 

  46. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002). Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science, 295, 858–861.

    Article  PubMed  CAS  Google Scholar 

  47. McNeill, L. A., Hewitson, K. S., Claridge, T. D., Seibel, J. F., Horsfall, L. E., & Schofield, C. J. (2002). Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the beta-carbon of asparagine-803. The Biochemical Journal, 367, 571–575.

    Article  PubMed  CAS  Google Scholar 

  48. Freedman, S. J., Sun, Z. Y., Poy, F., Kung, A. L., Livingston, D. M., Wagner, G., et al. (2002). Structural basis for recruitment of CBP/p300 by hypoxia-inducible factor-1 alpha. Proceedings of the National Academy of Sciences of the United States of America, 99, 5367–5372.

    Article  PubMed  CAS  Google Scholar 

  49. Dames, S. A., Martinez-Yamout, M., De Guzman, R. N., Dyson, H. J., & Wright, P. E. (2002). Structural basis for Hif-1 alpha/CBP recognition in the cellular hypoxic response. Proceedings of the National Academy of Sciences of the United States of America, 99, 5271–5276.

    Article  PubMed  CAS  Google Scholar 

  50. Wang, G. L., & Semenza, G. L. (1993). Desferrioxamine induces erythropoietin gene expression and hypoxia-inducible factor 1 DNA-binding activity: Implications for models of hypoxia signal transduction. Blood, 82, 3610–3615.

    PubMed  CAS  Google Scholar 

  51. Jiang, B. H., Jiang, G., Zheng, J. Z., Lu, Z., Hunter, T., & Vogt, P. K. (2001). Phosphatidylinositol 3-kinase signaling controls levels of hypoxia-inducible factor 1. Cell Growth & Differentiation, 12, 363–369.

    CAS  Google Scholar 

  52. Sandau, K. B., Faus, H. G., & Brüne, B. (2000). Induction of hypoxia-inducible-factor 1 by nitric oxide is mediated via the PI 3 K pathway. Biochemical and Biophysical Research Communications, 278, 263–267.

    Article  PubMed  CAS  Google Scholar 

  53. Treins, C., Giorgetti-Peraldi, S., Murdaca, J., Semenza, G. L., & Van Obberghen, E. (2002). Insulin stimulates hypoxia-inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. The Journal of Biological Chemistry, 277, 27975–27981.

    Article  PubMed  CAS  Google Scholar 

  54. Tramontano, A. F., Muniyappa, R., Black, A. D., Blendea, M. C., Cohen, I., Deng, L., et al. (2003). Erythropoietin protects cardiac myocytes from hypoxia-induced apoptosis through an Akt-dependent pathway. Biochem Biochemical and Biophysical Research Communications, 308, 990–994.

    Article  CAS  Google Scholar 

  55. Kim, C. H., Cho, Y. S., Chun, Y. S., Park, J. W., & Kim, M. S. (2002). Early expression of myocardial HIF-1alpha in response to mechanical stresses: Regulation by stretch-activated channels and the phosphatidylinositol 3-kinase signaling pathway. Circulation Research, 90, E25–E33.

    Article  PubMed  CAS  Google Scholar 

  56. Lee, S. H., Wolf, P. L., Escudero, R., Deutsch, R., Jamieson, S. W., & Thistlethwaite, P. A. (2000). Early expression of angiogenesis factors in acute myocardial ischemia and infarction. The New England Journal of Medicine, 342, 626–633.

    Article  PubMed  CAS  Google Scholar 

  57. Jurgensen, J. S., Rosenberger, C., Wiesener, M. S., Warnecke, C., Horstrup, J. H., Grafe, M., et al. (2004). Persistent induction of HIF-1alpha and -2alpha in cardiomyocytes and stromal cells of ischemic myocardium. FASEB Journal, 18, 1415–1417.

    PubMed  Google Scholar 

  58. Kido, M., Du, L., Sullivan, C. C., Li, X., Deutsch, R., Jamieson, S. W., et al. (2005). Hypoxia-inducible factor 1-alpha reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse. Journal of the American College of Cardiology, 46, 2116–2124.

    Article  PubMed  CAS  Google Scholar 

  59. Date, T., Mochizuki, S., Belanger, A. J., Yamakawa, M., Luo, Z., Vincent, K. A., et al. (2005). Expression of constitutively stable hybrid hypoxia-inducible factor-1alpha protects cultured rat cardiomyocytes against simulated ischemia-reperfusion injury. American Journal of Physiology. Cell Physiology, 288, C314–C320.

    Article  PubMed  CAS  Google Scholar 

  60. Kaelin, W. G., Jr, & Ratcliffe, P. J. (2008). Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Molecular Cell, 30, 393–402.

    Article  PubMed  CAS  Google Scholar 

  61. Berra, E., Benizri, E., Ginouves, A., Volmat, V., Roux, D., & Pouyssegur, J. (2003). HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. The EMBO Journal, 22, 4082–4090.

    Article  PubMed  CAS  Google Scholar 

  62. Minamishima, Y. A., Moslehi, J., Bardeesy, N., Cullen, D., Bronson, R. T., & Kaelin, W. G., Jr. (2008). Somatic inactivation of the PHD2 prolyl hydroxylase causes polycythemia and congestive heart failure. Blood, 111, 3236–3244.

    Article  PubMed  CAS  Google Scholar 

  63. Appelhoff, R. J., Tian, Y. M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., et al. (2004). Differential function of the prolyl hydroxylases PHD1, PHD2, and PHD3 in the regulation of hypoxia-inducible factor. The Journal of Biological Chemistry, 279, 38458–38465.

    Article  PubMed  CAS  Google Scholar 

  64. Minamishima, Y. A., Moslehi, J., Padera, R. F., Bronson, R. T., Liao, R., & Kaelin, W. G., Jr. (2009). A feedback loop involving the Phd3 prolyl hydroxylase tunes the mammalian hypoxic response in vivo. Molecular and Cellular Biology, 29, 5729–5741.

    Article  PubMed  CAS  Google Scholar 

  65. Huang, M., Chan, D. A., Jia, F., Xie, X., Li, Z., Hoyt, G., et al. (2008). Short hairpin RNA interference therapy for ischemic heart disease. Circulation, 118, S226–S233.

    Article  PubMed  CAS  Google Scholar 

  66. Lei, L., Mason, S., Liu, D., Huang, Y., Marks, C., Hickey, R., et al. (2008). Hypoxia-inducible factor-dependent degeneration, failure, and malignant transformation of the heart in the absence of the von Hippel-Lindau protein. Molecular and Cellular Biology, 28, 3790–3803.

    Article  PubMed  CAS  Google Scholar 

  67. Moslehi, J., Minamishima, Y. A., Shi, J., Neuberg, D., Charytan, D. M., Padera, R. F., et al. (2010). Loss of hypoxia-inducible factor prolyl hydroxylase activity in cardiomyocytes phenocopies ischemic cardiomyopathy. Circulation, 122, 1004–1016.

    Article  PubMed  CAS  Google Scholar 

  68. Bekeredjian, R., Walton, C. B., MacCannell, K. A., Ecker, J., Kruse, F., Outten, J. T., et al. (2010). Conditional HIF-1alpha expression produces a reversible cardiomyopathy. PLoS ONE, 5, e11693.

    Article  PubMed  Google Scholar 

  69. Giacca, M., & Zacchigna, S. (2012). VEGF gene therapy: Therapeutic angiogenesis in the clinic and beyond. Gene Therapy,. doi:10.1038.

    PubMed  Google Scholar 

  70. Eibel, B., Rodrigues, C. G., Giusti, I. I., Nesralla, I. A., Prates, P. R., Sant’Anna, R. T., et al. (2011). Gene therapy for ischemic heart disease: Review of clinical trials. The Revista Brasileira de Cirurgia Cardiovascular, 26, 635–646.

    Article  Google Scholar 

  71. Jeremy, J. Y., Shukla, N., Angelini, G. D., Day, A., Wan, I. Y., Talpahewa, S. P., et al. (2002). Sustained increases of plasma homocysteine, copper, and serum ceruloplasmin after coronary artery bypass grafting. The Annals of Thoracic Surgery, 74, 1553–1557.

    Article  PubMed  Google Scholar 

  72. Mansoor, M. A., Bergmark, C., Haswell, S. J., Savage, I. F., Evans, P. H., Berge, R. K., et al. (2000). Correlation between plasma total homocysteine and copper in patients with peripheral vascular disease. Clinical Chemistry, 46, 385–391.

    PubMed  CAS  Google Scholar 

  73. Shukla, N., Angelini, G. D., & Jeremy, J. Y. (2007). Interactive effects of homocysteine and copper on angiogenesis in porcine isolated saphenous vein. The Annals of Thoracic Surgery, 84, 43–49.

    Article  PubMed  Google Scholar 

  74. Apostolova, M. D., Bontchev, P. R., Ivanova, B. B., Russell, W. R., Mehandjiev, D. R., Beattie, J. H., et al. (2003). Copper-homocysteine complexes and potential physiological actions. Journal of Inorganic Biochemistry, 95, 321–333.

    Article  PubMed  CAS  Google Scholar 

  75. Carrasco-Pozo, C., Alvarez-Lueje, A., Olea-Azar, C., Lopez-Alarcon, C., & Speisky, H. (2006). In vitro interaction between homocysteine and copper ions: Potential redox implications. Experimental Biology and Medicine (Maywood, NJ), 231, 1569–1575.

    CAS  Google Scholar 

  76. Emsley, A. M., Jeremy, J. Y., Gomes, G. N., Angelini, G. D., & Plane, F. (1999). Investigation of the inhibitory effects of homocysteine and copper on nitric oxide-mediated relaxation of rat isolated aorta. British Journal of Pharmacology, 126, 1034–1040.

    Article  PubMed  CAS  Google Scholar 

  77. Linnebank, M., Lutz, H., Jarre, E., Vielhaber, S., Noelker, C., Struys, E., et al. (2006). Binding of copper is a mechanism of homocysteine toxicity leading to COX deficiency and apoptosis in primary neurons, PC12 and SHSY-5Y cells. Neurobiology of Disease, 23, 725–730.

    Article  PubMed  CAS  Google Scholar 

  78. Martin, F., Linden, T., Katschinski, D. M., Oehme, F., Flamme, I., Mukhopadhyay, C. K., et al. (2005). Copper-dependent activation of hypoxia-inducible factor (HIF)-1: Implications for ceruloplasmin regulation. Blood, 105, 4613–4619.

    Article  PubMed  CAS  Google Scholar 

  79. van Heerden, D., Vosloo, A., & Nikinmaa, M. (2004). Effects of short-term copper exposure on gill structure, metallothionein and hypoxia-inducible factor-1alpha (HIF-1alpha) levels in rainbow trout (Oncorhynchus mykiss). Aquatic Toxicology, 69, 271–280.

    Article  PubMed  Google Scholar 

  80. Jiang, Y., Reynolds, C., Xiao, C., Feng, W., Zhou, Z., Rodriguez, W., et al. (2007). Dietary copper supplementation reverses hypertrophic cardiomyopathy induced by chronic pressure overload in mice. The Journal of Experimental Medicine, 204, 657–666.

    Article  PubMed  CAS  Google Scholar 

  81. Ziche, M., Jones, J., & Gullino, P. M. (1982). Role of prostaglandin E1 and copper in angiogenesis. Journal of the National Cancer Institute, 69, 475–482.

    PubMed  CAS  Google Scholar 

  82. Harris, E. D. (2004). A requirement for copper in angiogenesis. Nutrition Reviews, 62, 60–64.

    Article  PubMed  Google Scholar 

  83. Lowndes, S. A., & Harris, A. L. (2005). The role of copper in tumour angiogenesis. Journal of Mammary Gland Biology and Neoplasia, 10, 299–310.

    Article  PubMed  Google Scholar 

  84. Nasulewicz, A., Mazur, A., & Opolski, A. (2004). Role of copper in tumour angiogenesis–clinical implications. Journal of Trace Elements in Medicine and Biology, 18, 1–8.

    Article  PubMed  CAS  Google Scholar 

  85. Goodman, V. L., Brewer, G. J., & Merajver, S. D. (2005). Control of copper status for cancer therapy. Current Cancer Drug Targets, 5, 543–549.

    Article  PubMed  CAS  Google Scholar 

  86. Sen, C. K., Khanna, S., Venojarvi, M., Trikha, P., Ellison, E. C., Hunt, T. K., et al. (2002). Copper-induced vascular endothelial growth factor expression and wound healing. American Journal of Physiology: Heart and Circulatory Physiology, 282, H1821–H1827.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Regenerative Medicine Research Center, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, People’s Republic of China

    Weihong He & Y. James Kang

  2. Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, 40292, USA

    Y. James Kang

Authors
  1. Weihong He
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. James Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. James Kang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

He, W., James Kang, Y. Ischemia-induced Copper Loss and Suppression of Angiogenesis in the Pathogenesis of Myocardial Infarction. Cardiovasc Toxicol 13, 1–8 (2013). https://doi.org/10.1007/s12012-012-9174-y

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-012-9174-y

Keywords

Search

Navigation