About this Journal Submit a Manuscript Table of Contents
BioMed Research International
Volume 2013 (2013), Article ID 437613, 15 pages
http://dx.doi.org/10.1155/2013/437613
Review Article

Molecular Basis of Cardioprotective Effect of Antioxidant Vitamins in Myocardial Infarction

Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Independencia 1027, Casilla 70058, Santiago 7, Chile

Received 30 April 2013; Accepted 18 June 2013

Academic Editor: Claiton Leonetti Lencina

Copyright © 2013 Ramón Rodrigo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. A. A. Fox, P. G. Steg, K. A. Eagle et al., “Decline in rates of death and heart failure in acute coronary syndromes, 1999–2006,” Journal of the American Medical Association, vol. 297, no. 17, pp. 1892–1900, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. M. I. Furman, H. L. Dauerman, R. J. Goldberg, J. Yarzebski, D. Lessard, and J. M. Gore, “Twenty-two year (1975 to 1997) trends in the incidence, in-hospital and long-term case fatality rates from initial Q-wave and non-Q-wave myocardial infarction: a multi-hospital, community-wide perspective,” Journal of the American College of Cardiology, vol. 37, no. 6, pp. 1571–1580, 2001. View at Publisher · View at Google Scholar · View at Scopus
  3. R. Liew, S. Sulfi, K. Ranjadayalan, J. Cooper, and A. D. Timmis, “Declining case fatality rates for acute myocardial infarction in South Asian and white patients in the past 15 years,” Heart, vol. 92, no. 8, pp. 1030–1034, 2006. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Mandelzweig, A. Battler, V. Boyko et al., “The second euro heart survey on acute coronary syndromes: characteristics, treatment, and outcome of patients with ACS in Europe and the Mediterranean Basin in 2004,” European Heart Journal, vol. 27, no. 19, pp. 2285–2293, 2006. View at Publisher · View at Google Scholar · View at Scopus
  5. S. R. J. Maxwell, “Anti-oxidant therapy: does it have a role in the treatment of human disease?” Expert Opinion on Investigational Drugs, vol. 6, no. 3, pp. 211–236, 1997. View at Publisher · View at Google Scholar · View at Scopus
  6. M. Hori and K. Nishida, “Oxidative stress and left ventricular remodelling after myocardial infarction,” Cardiovascular Research, vol. 81, no. 3, pp. 457–464, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. D. M. Yellon and D. J. Hausenloy, “Myocardial reperfusion injury,” The New England Journal of Medicine, vol. 357, no. 11, pp. 1074–1135, 2007. View at Publisher · View at Google Scholar · View at Scopus
  8. T. S. Jackson, A. Xu, J. A. Vita, and J. F. Keaney Jr., “Ascorbate prevents the interaction of superoxide and nitric oxide only at very high physiological concentrations,” Circulation Research, vol. 83, no. 9, pp. 916–922, 1998. View at Scopus
  9. D. J. Hausenloy and D. M. Yellon, “Myocardial ischemia-reperfusion injury: a neglected therapeutic target,” The Journal of Clinical Investigation, vol. 123, pp. 92–100, 2013.
  10. K. Tsovolas, E. K. Iliodromitis, I. Andreadou et al., “Acute administration of vitamin C abrogates protection from ischemic preconditioning in rabbits,” Pharmacological Research, vol. 57, no. 4, pp. 283–289, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. M. I. Furman, H. L. Dauerman, R. J. Goldberg, J. Yarzebski, D. Lessard, and J. M. Gore, “Pharmacokinetics of vitamin C: insights into the oral and intravenous administration of ascorbate,” Puerto Rico Health Sciences Journal, vol. 27, no. 1, pp. 7–19, 2008. View at Scopus
  12. S. J. Padayatty, A. Y. Sun, Q. Chen, M. G. Espey, J. Drisko, and M. Levine, “Vitamin C: intravenous use by complementary and alternative medicine practitioners and adverse effects,” PLoS ONE, vol. 5, no. 7, Article ID e11414, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. I. Juránek and Š. Bezek, “Controversy of free radical hypothesis: reactive oxygen species—cause or consequence of tissue injury,” General Physiology and Biophysics, vol. 24, no. 3, pp. 263–278, 2005. View at Scopus
  14. K. M. Venardos, A. Perkins, J. Headrick, and D. M. Kaye, “Myocardial ischemia-reperfusion injury, antioxidant enzyme systems, and selenium: a review,” Current Medicinal Chemistry, vol. 14, pp. 1539–1549, 2007.
  15. R. Rodrigo, J. C. Prieto, and R. Castillo, “Cardioprotection against ischaemia/reperfusion by vitamins C and E plus n-3 fatty acids: molecular mechanisms and potential clinical applications,” Clinical Science, vol. 124, pp. 1–15, 2013.
  16. N. R. Perron and J. L. Brumaghim, “A review of the antioxidant mechanisms of polyphenol compounds related to iron binding,” Cell Biochemistry and Biophysics, vol. 53, no. 2, pp. 75–100, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. T. Jaxa-Chamiec, B. Bednarz, D. Drozdowska et al., “Antioxidant effects of combined vitamins C and E in acute myocardial infarction. The randomized, double-blind, placebo controlled, multicenter pilot myocardial infarction and VITamins (MIVIT) trial,” Kardiologia Polska, vol. 62, no. 4, pp. 344–350, 2005. View at Scopus
  18. T. Jaxa-Chamiec, B. Bednarz, K. Herbaczynska-Cedro, P. Maciejewski, and L. Ceremuzynski, “Effects of vitamins C and E on the outcome after acute myocardial infarction in diabetics: a retrospective, hypothesis-generating analysis from the MIVIT Study,” Cardiology, vol. 112, no. 3, pp. 219–223, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. B. Bednarz, T. Chamiec, and L. Ceremuzyńiski, “Antioxidant vitamins decrease exercise-induced QT dispersion after myocardial infarction,” Kardiologia Polska, vol. 58, no. 5, pp. 375–379, 2003. View at Scopus
  20. R. B. Singh, M. A. Niaz, S. S. Rastogi, and S. Rastogi, “Usefulness of antioxidant vitamins in suspected acute myocardial infarction (the Indian Experiment of Infarct Survival-3),” American Journal of Cardiology, vol. 77, no. 4, pp. 232–236, 1996. View at Publisher · View at Google Scholar · View at Scopus
  21. T. Chamiec, K. Herbaczyńska-Cedro, and L. Ceremuzyński, “Effects of antioxidant vitamins C and E on signal-averaged electrocardiogram in acute myocardial infarction,” The American Journal of Cardiology, vol. 77, pp. 237–241, 1996.
  22. R. B. Singh, G. S. Wander, A. Rastogi, et al., “Randomized, double-blind placebo-controlled trial of coenzyme Q10 in patients with acute myocardial infarction,” Cardiovascular Drugs and Therapy, vol. 12, pp. 347–353, 1998.
  23. R. B. Singh, M. A. Niaz, P. Agarwal, R. Beegum, S. S. Rastogi, and D. S. Sachan, “A randomised, double-blind, placebo-controlled trial of L-carnitine in suspected acute myocardial infarction,” Postgraduate Medical Journal, vol. 72, no. 843, pp. 45–50, 1996. View at Scopus
  24. H. Thiele, L. Hildebrand, C. Schirdewahn et al., “Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial,” Journal of the American College of Cardiology, vol. 55, no. 20, pp. 2201–2209, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. K. Tsujita, H. Shimomura, K. Kaikita et al., “Long-term efficacy of edaravone in patients with acute myocardial infarction,” Circulation Journal, vol. 70, no. 7, pp. 832–837, 2006. View at Publisher · View at Google Scholar · View at Scopus
  26. J. T. Flaherty, B. Pitt, J. W. Gruber et al., “Recombinant human superoxide dismutase (h-SOD) fails to improve recovery of ventricular function in patients undergoing coronary angioplasty for acute myocardial infarction,” Circulation, vol. 89, no. 5, pp. 1982–1991, 1994. View at Scopus
  27. W. Guan, T. Osanai, T. Kamada et al., “Effect of allopurinol pretreatment on free radical generation after primary coronary angioplasty for acute myocardial infarction,” Journal of Cardiovascular Pharmacology, vol. 41, no. 5, pp. 699–705, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Yunoki, T. Naruko, K. Sugioka, et al., “Erythrocyte-rich thrombus aspirated from patients with ST-elevation myocardial infarction: association with oxidative stress and its impact on myocardial reperfusion,” European Heart Journal, vol. 33, pp. 1480–1490, 2012.
  29. P. Eaton and H. Clements-Jewery, “Peroxynitrite: in vivo cardioprotectant or arrhythmogen?” British Journal of Pharmacology, vol. 155, no. 7, pp. 972–973, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. L. Wang, G. D. Lopaschuk, and A. S. Clanachan, “H2O2-induced left ventricular dysfunction in isolated working rat hearts is independent of calcium accumulation,” Journal of Molecular and Cellular Cardiology, vol. 45, no. 6, pp. 787–795, 2008. View at Publisher · View at Google Scholar · View at Scopus
  31. M. Avkiran and M. S. Marber, “Na+/H+ exchange inhibitors for cardioprotective therapy: progress, problems and prospects,” Journal of the American College of Cardiology, vol. 39, no. 5, pp. 747–753, 2002. View at Publisher · View at Google Scholar · View at Scopus
  32. C. Duilio, G. Ambrosio, P. Kuppusamy, A. Dipaula, L. C. Becker, and J. L. Zweier, “Neutrophils are primary source of O2 radicals during reperfusion after prolonged myocardial ischemia,” American Journal of Physiology, vol. 280, no. 6, pp. H2649–H2657, 2001. View at Scopus
  33. N. G. Frangogiannis, C. W. Smith, and M. L. Entman, “The inflammatory response in myocardial infarction,” Cardiovascular Research, vol. 53, no. 1, pp. 31–47, 2002. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Ferdinandy, H. Danial, I. Ambrus, R. A. Rothery, and R. Schulz, “Peroxynitrite is a major contributor to cytokine-induced myocardial contractile failure,” Circulation Research, vol. 87, no. 3, pp. 241–247, 2000. View at Scopus
  35. N. Suematsu, H. Tsutsui, J. Wen et al., “Oxidative stress mediates tumor necrosis factor-α-induced mitochondrial DNA damage and dysfunction in cardiac myocytes,” Circulation, vol. 107, no. 10, pp. 1418–1423, 2003. View at Publisher · View at Google Scholar · View at Scopus
  36. D. A. Siwik, P. J. Pagano, and W. S. Colucci, “Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts,” American Journal of Physiology, vol. 280, no. 1, pp. C53–C60, 2001. View at Scopus
  37. A. Deten, A. Hölzl, M. Leicht, W. Barth, and H.-G. Zimmer, “Changes in extracellular matrix and in transforming growth factor beta isoforms after coronary artery ligation in rats,” Journal of Molecular and Cellular Cardiology, vol. 33, no. 6, pp. 1191–1207, 2001. View at Publisher · View at Google Scholar · View at Scopus
  38. L. E. Rohde, A. Ducharme, L. H. Arroyo, et al., “Matrix metalloproteinase inhibition attenuates early left Ventricular injury,” Cardiovascular Research, vol. 47, pp. 446–456, 2000.
  39. R. Bolli and E. Marbán, “Molecular and cellular mechanisms of myocardial stunning,” Physiological Reviews, vol. 79, pp. 609–634, 1999.
  40. R. Ferrari, “The role of Mitochondria in ischemic heart disease,” Journal of Cardiovascular Pharmacology, vol. 28, no. 1, pp. S1–S10, 1996. View at Scopus
  41. A. Jahangiri, W. R. Leifert, K. L. Kind, and E. J. McMurchie, “Dietary fish oil alters cardiomyocyte Ca2+ dynamics and antioxidant status,” Free Radical Biology and Medicine, vol. 40, no. 9, pp. 1592–1602, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. L. C. Hool, “Evidence for the regulation of L-type Ca2+ channels in the heart by reactive oxygen species: mechanism for mediating pathology,” Clinical and Experimental Pharmacology and Physiology, vol. 35, no. 2, pp. 229–234, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. I. M. C. Dixon, T. Hata, and N. S. Dhalla, “Sarcolemmal Na+-K+-ATPase activity in congestive heart failure due to myocardial infarction,” American Journal of Physiology, vol. 262, no. 3, pp. C664–C671, 1992. View at Scopus
  44. M. Sasaki and T. Joh, “Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents,” Journal of Clinical Biochemistry and Nutrition, vol. 40, no. 1, pp. 1–12, 2007. View at Publisher · View at Google Scholar · View at Scopus
  45. J. R. Egan, T. L. Butler, A. D. Cole et al., “Myocardial membrane injury in pediatric cardiac surgery: an animal model,” Journal of Thoracic and Cardiovascular Surgery, vol. 137, no. 5, pp. 1154–1162, 2009. View at Publisher · View at Google Scholar · View at Scopus
  46. T. Scarabelli, A. Stephanou, N. Rayment et al., “Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischemia/reperfusion injury,” Circulation, vol. 104, no. 3, pp. 253–256, 2001. View at Scopus
  47. S. Vandervelde, M. J. A. van Luyn, M. H. Rozenbaum, A. H. Petersen, R. A. Tio, and M. C. Harmsen, “Stem cell-related cardiac gene expression early after murine myocardial infarction,” Cardiovascular Research, vol. 73, no. 4, pp. 783–793, 2007. View at Publisher · View at Google Scholar · View at Scopus
  48. B. Chandrasekar, J. B. Smith, and G. L. Freeman, “Ischemia-reperfusion of rat myocardium activates nuclear factor-κb and induces neutrophil infiltration via lipopolysaccharide-induced CXC chemokine,” Circulation, vol. 103, no. 18, pp. 2296–2302, 2001. View at Scopus
  49. D. Cooper, K. Y. Stokes, A. Tailor, and D. N. Granger, “Oxidative stress promotes blood cell-endothelial cell interactions in the microcirculation,” Cardiovascular Toxicology, vol. 2, no. 3, pp. 165–180, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. M. Pavelková, L. Kubala, M. Cíz, et al., “Blood phagocyte activation during open heart surgery with cardiopulmonary bypass,” Physiological Research, vol. 55, pp. 165–173, 2006.
  51. R. Kohen and A. Nyska, “Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification,” Toxicologic Pathology, vol. 30, no. 6, pp. 620–650, 2002. View at Publisher · View at Google Scholar · View at Scopus
  52. T. Kinoshita, T. Asai, N. Takashima et al., “Preoperative C-reactive protein and atrial fibrillation after off-pump coronary bypass surgery,” European Journal of Cardio-thoracic Surgery, vol. 40, no. 6, pp. 1298–1303, 2011. View at Publisher · View at Google Scholar · View at Scopus
  53. A. Valtchanova-Matchouganska, M. Gondwe, and A. Nadar, “The role of C-reactive protein in ischemia/reperfusion injury and preconditioning in a rat model of myocardial infarction,” Life Sciences, vol. 75, no. 8, pp. 901–910, 2004. View at Publisher · View at Google Scholar · View at Scopus
  54. J. J. Lemasters, J. M. Bond, E. Chacon et al., “The pH paradox in ischemia-reperfusion injury to cardiac myocytes,” EXS, vol. 76, pp. 99–114, 1996. View at Scopus
  55. J. M. Bond, B. Herman, and J. J. Lemasters, “Protection by acidotic pH against anoxia/reoxygenation injury to rat neonatal cardiac myocytes,” Biochemical and Biophysical Research Communications, vol. 179, no. 2, pp. 798–803, 1991. View at Scopus
  56. J. J. Lemasters, T. P. Theruvath, Z. Zhong, and A.-L. Nieminen, “Mitochondrial calcium and the permeability transition in cell death,” Biochimica et Biophysica Acta, vol. 1787, no. 11, pp. 1395–1401, 2009. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Miyamae, S. A. Camacho, M. W. Weiner, and V. M. Figueredo, “Attenuation of postischemic reperfusion injury is related to prevention of [Ca2+](m) overload in rat hearts,” American Journal of Physiology, vol. 271, no. 5, pp. H2145–H2153, 1996. View at Scopus
  58. S. Orrenius, D. J. McConkey, G. Bellomo, and P. Nicotera, “Role of Ca2+ in toxic cell killing,” Trends in Pharmacological Sciences, vol. 10, no. 7, pp. 281–285, 1989. View at Scopus
  59. P. Milberg, M. Fink, C. Pott et al., “Blockade of ICa suppresses early afterdepolarizations and reduces transmural dispersion of repolarization in a whole heart model of chronic heart failure,” British Journal of Pharmacology, vol. 166, no. 2, pp. 557–568, 2012. View at Publisher · View at Google Scholar · View at Scopus
  60. D. J. Hausenloy and D. M. Yellon, “The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion,” Journal of Molecular and Cellular Cardiology, vol. 35, no. 4, pp. 339–341, 2003. View at Publisher · View at Google Scholar · View at Scopus
  61. G. Heusch, K. Boengler, and R. Schulz, “Inhibition of mitochondrial permeability transition pore opening: the holy grail of cardioprotection,” Basic Research in Cardiology, vol. 105, no. 2, pp. 151–154, 2010. View at Publisher · View at Google Scholar · View at Scopus
  62. E. J. Griffiths and A. P. Halestrap, “Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion,” Biochemical Journal, vol. 307, no. 1, pp. 93–98, 1995. View at Scopus
  63. H. Otani, “Reactive oxygen species as mediators of signal transduction in ischemic preconditioning,” Antioxidants and Redox Signaling, vol. 6, no. 2, pp. 449–469, 2004. View at Publisher · View at Google Scholar · View at Scopus
  64. R. von Harsdorf, P.-F. Li, and R. Dietz, “Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis,” Circulation, vol. 99, no. 22, pp. 2934–2941, 1999. View at Scopus
  65. Y. Dun, J.-M. Zhi, H.-Y. Sun, R.-R. Zhao, and Z.-Q. Zhao, “Activated polymorphonuclear leukocytes induce cardiomyocyte apoptosis and the protective effects of carvedilol,” Methods and Findings in Experimental and Clinical Pharmacology, vol. 24, no. 7, pp. 403–412, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. A. E. Vendrov, Z. S. Hakim, N. R. Madamanchi, M. Rojas, C. Madamanchi, and M. S. Runge, “Atherosclerosis is attenuated by limiting superoxide generation in both macrophages and vessel wall cells,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 27, no. 12, pp. 2714–2721, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. H. Jay Forman and M. Torres, “Redox signaling in macrophages,” Molecular Aspects of Medicine, vol. 22, no. 4-5, pp. 189–216, 2001. View at Publisher · View at Google Scholar · View at Scopus
  68. Z.-Q. Zhao, D. A. Velez, N.-P. Wang et al., “Progressively developed myocardial apoptotic cell death during late phase of reperfusion,” Apoptosis, vol. 6, no. 4, pp. 279–290, 2001. View at Publisher · View at Google Scholar · View at Scopus
  69. H. Nakajima, N. Mizuta, I. Fujiwara et al., “Blockade of the Fas/Fas ligand interaction suppresses hepatocyte apoptosis in ischemia-reperfusion rat liver,” Apoptosis, vol. 13, no. 8, pp. 1013–1021, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. A. Van Dijk, P. A. J. Krijnen, R. A. Vermond et al., “Inhibition of type 2A secretory phospholipase A2 reduces death of cardiomyocytes in acute myocardial infarction,” Apoptosis, vol. 14, no. 6, pp. 753–763, 2009. View at Publisher · View at Google Scholar · View at Scopus
  71. Y. Matsui, H. Takagi, X. Qu et al., “Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and beclin 1 in mediating autophagy,” Circulation Research, vol. 100, no. 6, pp. 914–922, 2007. View at Publisher · View at Google Scholar · View at Scopus
  72. C. P. Baines, R. A. Kaiser, N. H. Purcell et al., “Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death,” Nature, vol. 434, no. 7033, pp. 658–662, 2005. View at Publisher · View at Google Scholar · View at Scopus
  73. C. P. Gale, E. Metcalfe, R. M. West et al., “An Assessment of the concentration-related prognostic value of cardiac troponin i following acute coronary syndrome,” American Journal of Cardiology, vol. 108, no. 9, pp. 1259–1265, 2011. View at Publisher · View at Google Scholar · View at Scopus
  74. S. M. Dallabrida, N. Ismail, J. R. Oberle, B. E. Himes, and M. A. Rupnick, “Angiopoietin-1 promotes cardiac and skeletal myocyte survival through integrins,” Circulation Research, vol. 96, no. 4, pp. e8–e24, 2005. View at Scopus
  75. R. S. Whelan, V. Kaplinskiy, and R. N. Kitsis, “Cell death in the pathogenesis of heart disease: mechanisms and significance,” Annual Review of Physiology, vol. 72, pp. 19–44, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. C. Communal, M. Sumandea, P. De Tombe, J. Narula, R. J. Solaro, and R. J. Hajjar, “Functional consequences of caspase activation in cardiac myocytes,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 9, pp. 6252–6256, 2002. View at Publisher · View at Google Scholar · View at Scopus
  77. T. Singh, S. D. Sharma, and S. K. Katiyar, “Grape proanthocyanidins induce apoptosis by loss of mitochondrial membrane potential of human non-small cell lung cancer cells In Vitro and In Vivo,” PLoS ONE, vol. 6, no. 11, Article ID e27444, 2011. View at Publisher · View at Google Scholar · View at Scopus
  78. C. Adrain and S. J. Martin, “The mitochondrial apoptosome: a killer unleashed by the cytochrome seas,” Trends in Biochemical Sciences, vol. 26, no. 6, pp. 390–397, 2001. View at Publisher · View at Google Scholar · View at Scopus
  79. C. Candé, I. Cohen, E. Daugas et al., “Apoptosis-inducing factor (AIF): a novel caspase-independent death effector released from mitochondria,” Biochimie, vol. 84, no. 2-3, pp. 215–222, 2002. View at Publisher · View at Google Scholar · View at Scopus
  80. P. Lee, M. Sata, D. J. Lefer, S. M. Factor, K. Walsh, and R. N. Kitsis, “Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo,” American Journal of Physiology, vol. 284, no. 2, pp. H456–H463, 2003. View at Scopus
  81. T. Nakamura, L. Wang, C. C. L. Wong et al., “Transnitrosylation of XIAP regulates caspase-dependent neuronal cell death,” Molecular Cell, vol. 39, no. 2, pp. 184–195, 2010. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Tatsumi, J. Shiraishi, N. Keira et al., “Intracellular ATP is required for mitochondrial apoptotic pathways in isolated hypoxic rat cardiac myocytes,” Cardiovascular Research, vol. 59, no. 2, pp. 428–440, 2003. View at Publisher · View at Google Scholar · View at Scopus
  83. M. N. Quinsay, R. L. Thomas, Y. Lee, and Å. B. Gustafsson, “Bnip3-mediated mitochondrial autophagy is independent of the mitochondrial permeability transition pore,” Autophagy, vol. 6, no. 7, pp. 855–862, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. D.-F. Dai and P. Rabinovitch, “Mitochondrial oxidative stress mediates induction of autophagy and hypertrophy in angiotensin-II treated mouse hearts,” Autophagy, vol. 7, no. 8, pp. 917–918, 2011. View at Publisher · View at Google Scholar · View at Scopus
  85. N. Hariharan, P. Zhai, and J. Sadoshima, “Oxidative stress stimulates autophagic flux during ischemia/reperfusion,” Antioxidants and Redox Signaling, vol. 14, no. 11, pp. 2179–2190, 2011. View at Publisher · View at Google Scholar · View at Scopus
  86. E. E. Essick and F. Sam, “Oxidative stress and autophagy in cardiac disease, neurological disorders, aging and cancer,” Oxidative Medicine and Cellular Longevity, vol. 3, no. 3, pp. 168–177, 2010. View at Publisher · View at Google Scholar · View at Scopus
  87. M. Ushio-Fukai, “Compartmentalization of redox signaling through NaDPH oxidase-derived rOS,” Antioxidants and Redox Signaling, vol. 11, no. 6, pp. 1289–1299, 2009. View at Publisher · View at Google Scholar · View at Scopus
  88. Y. Matsui, S. Kyoi, H. Takagi et al., “Molecular mechanisms and physiological significance of autophagy during myocardial ischemia and reperfusion,” Autophagy, vol. 4, no. 4, pp. 409–415, 2008. View at Scopus
  89. M. Juhaszova, D. B. Zorov, S.-H. Kim et al., “Glycogen synthase kinase-3β mediates convergence of protection signalling to inhibit the mitochondrial permeability transition pore,” Journal of Clinical Investigation, vol. 113, no. 11, pp. 1535–1549, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. H. Zhu, P. Tannous, J. L. Johnstone et al., “Cardiac autophagy is a maladaptive response to hemodynamic stress,” Journal of Clinical Investigation, vol. 117, no. 7, pp. 1782–1793, 2007. View at Publisher · View at Google Scholar · View at Scopus
  91. L. Yan, J. Sadoshima, D. E. Vatner, and S. F. Vatner, “Autophagy in ischemic preconditioning and hibernating myocardium,” Autophagy, vol. 5, no. 5, pp. 709–712, 2009. View at Publisher · View at Google Scholar · View at Scopus
  92. L. Zhou, A. Azfer, J. Niu et al., “Monocyte chemoattractant protein-1 induces a novel transcription factor that causes cardiac myocyte apoptosis and ventricular dysfunction,” Circulation Research, vol. 98, no. 9, pp. 1177–1185, 2006. View at Publisher · View at Google Scholar · View at Scopus
  93. C. W. Younce and P. E. Kolattukudy, “MCP-1 causes cardiomyoblast death via autophagy resulting from ER stress caused by oxidative stress generated by inducing a novel zinc-finger protein, MCPIP,” Biochemical Journal, vol. 426, no. 1, pp. 43–53, 2010. View at Publisher · View at Google Scholar · View at Scopus
  94. J. M. Upston, P. K. Witting, A. J. Brown, R. Stocker, and J. F. Keaney Jr., “Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits,” Free Radical Biology and Medicine, vol. 31, no. 10, pp. 1245–1253, 2001. View at Publisher · View at Google Scholar · View at Scopus
  95. A. C. Terentis, S. R. Thomas, J. A. Burr, D. C. Liebler, and R. Stocker, “Vitamin E oxidation in human atherosclerotic lesions,” Circulation Research, vol. 90, no. 3, pp. 333–339, 2002. View at Publisher · View at Google Scholar · View at Scopus
  96. H. Shi, N. Noguchi, and E. Niki, “Comparative study on dynamics of antioxidative action of α-tocopheryl hydroquinone, ubiquinol, and α-tocopherol against lipid peroxidation,” Free Radical Biology and Medicine, vol. 27, no. 3-4, pp. 334–346, 1999. View at Publisher · View at Google Scholar · View at Scopus
  97. R. Brigelius-Flohé, F. J. Kelly, J. T. Salonen, J. Neuzil, J.-M. Zingg, and A. Azzi, “The European perspective on vitamin E: current knowledge and future research,” American Journal of Clinical Nutrition, vol. 76, no. 4, pp. 703–716, 2002. View at Scopus
  98. R.-K. Li, D. B. Cowan, D. A. G. Mickle, R. D. Weisel, and G. W. Burton, “Effect of vitamin E on human glutathione peroxidase (GSH-Px1) expression in cardiomyocytes,” Free Radical Biology and Medicine, vol. 21, no. 4, pp. 419–426, 1996. View at Publisher · View at Google Scholar · View at Scopus
  99. S. Ülker, P. P. McKeown, and U. Bayraktutan, “Vitamins reverse endothelial dysfunction through regulation of eNOS and NAD(P)H oxidase activities,” Hypertension, vol. 41, no. 3, pp. 534–539, 2003. View at Publisher · View at Google Scholar · View at Scopus
  100. T. Nakamura, M. Goto, A. Matsumoto, and I. Tanaka, “Inhibition of NF-κB transcriptional activity by α-tocopheryl succinate,” BioFactors, vol. 7, no. 1-2, pp. 21–30, 1998. View at Scopus
  101. M. Kaileh and R. Sen, “Role of NF-kappaB in the anti-inflammatory effects of tocotrienols,” Journal of the American College of Nutrition, vol. 29, pp. 334–339, 2010.
  102. I. Jialal, M. Traber, and S. Devaraj, “Is there a vitamin E paradox?” Current Opinion in Lipidology, vol. 12, pp. 49–53, 2001.
  103. H. Rabl, G. Koschsorur, and W. Petek, “Antioxidant vitamin treatment: effect on lipid peroxidation and limb swelling after revascularisation operations,” World Journal of Surgery, vol. 19, pp. 738–744, 1995.
  104. H. Rabl, G. Khoschsorur, T. Colombo et al., “A multivitamin infusion prevents lipid peroxidation and improves transplantation performance,” Kidney International, vol. 43, no. 4, pp. 912–917, 1993. View at Scopus
  105. H. Cerwenka, H. Bacher, G. Werkgartner et al., “Antioxidant treatment during liver resection for alleviation of ischemia-reperfusion injury,” Hepato-Gastroenterology, vol. 45, no. 21, pp. 777–782, 1998. View at Scopus
  106. M. H. W. A. Wijnen, R. M. H. Roumen, H. L. Vader, and R. J. A. Goris, “A multiantioxidant supplementation reduces damage from ischaemia reperfusion in patients after lower torso ischaemia. A randomised trial,” European Journal of Vascular and Endovascular Surgery, vol. 23, no. 6, pp. 486–490, 2002. View at Publisher · View at Google Scholar · View at Scopus
  107. M. Bartels, H. K. Biesalski, K. Engelhart, G. Sendlhofer, P. Rehak, and E. Nagel, “Pilot study on the effect of parenteral vitamin E on ischemia and reperfusion induced liver injury: a double blind, randomized, placebo-controlled trial,” Clinical Nutrition, vol. 23, no. 6, pp. 1360–1370, 2004. View at Publisher · View at Google Scholar · View at Scopus
  108. M. Levine, S. Padayatty, and M. E. Graham, “Vitamin C: a concentration-function approach yields pharmacology and therapeutic discoveries,” Advances in Nutrition, vol. 2, pp. 78–88, 2011.
  109. C. P. Corpe, H. Tu, P. Eck et al., “Vitamin C transporter Slc23a1 links renal reabsorption, vitamin C tissue accumulation, and perinatal survival in mice,” Journal of Clinical Investigation, vol. 120, no. 4, pp. 1069–1083, 2010. View at Publisher · View at Google Scholar · View at Scopus
  110. C. I. Rivas, F. A. Zúñiga, A. Salas-Burgos, L. Mardones, V. Ormazabal, and J. C. Vera, “Vitamin C transporters,” Journal of Physiology and Biochemistry, vol. 64, no. 4, pp. 357–376, 2008. View at Publisher · View at Google Scholar · View at Scopus
  111. M. A. Pfeffer, E. Braunwald, L. A. Moye et al., “Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction—results of the survival and ventricular enlargement trial,” The New England Journal of Medicine, vol. 327, no. 10, pp. 669–677, 1992. View at Scopus
  112. M. Jensen-Urstad, B. A. Samad, K. Jensen-Urstad et al., “Risk assessment in patients with acute myocardial infarction treated with thrombolytic therapy,” Journal of Internal Medicine, vol. 249, no. 6, pp. 527–537, 2001. View at Publisher · View at Google Scholar · View at Scopus
  113. H. Takanaga, B. Mackenzie, and M. A. Hediger, “Sodium-dependent ascorbic acid transporter family SLC23,” Pflugers Archiv European Journal of Physiology, vol. 447, no. 5, pp. 677–682, 2004. View at Publisher · View at Google Scholar · View at Scopus
  114. M. Grover-McKay, S. A. Walsh, and S. A. Thompson, “Glucose transporter 3 (GLUT3) protein is present in human myocardium,” Biochimica et Biophysica Acta, vol. 1416, no. 1-2, pp. 145–154, 1999. View at Publisher · View at Google Scholar · View at Scopus
  115. I. Savini, A. Rossi, C. Pierro, L. Avigliano, and M. V. Catani, “SVCT1 and SVCT2: key proteins for vitamin C uptake,” Amino Acids, vol. 34, no. 3, pp. 347–355, 2008. View at Publisher · View at Google Scholar · View at Scopus
  116. D. P. Rajan, W. Huang, B. Dutta et al., “Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function,” Biochemical and Biophysical Research Communications, vol. 262, no. 3, pp. 762–768, 1999. View at Publisher · View at Google Scholar · View at Scopus
  117. V. H. Guaiquil, D. W. Golde, D. L. Beckles, E. J. Mascareno, and M. A. Q. Siddiqui, “Vitamin C inhibits hypoxia-induced damage and apoptotic signaling pathways in cardiomyocytes and ischemic hearts,” Free Radical Biology and Medicine, vol. 37, no. 9, pp. 1419–1429, 2004. View at Publisher · View at Google Scholar · View at Scopus
  118. S. J. Padayatty, A. Katz, Y. Wang et al., “Vitamin C as an antioxidant: evaluation of its role in disease prevention,” Journal of the American College of Nutrition, vol. 22, no. 1, pp. 18–35, 2003. View at Scopus
  119. F. Gao, C.-L. Yao, E. Gao et al., “Enhancement of glutathione cardioprotection by ascorbic acid in myocardial reperfusion injury,” Journal of Pharmacology and Experimental Therapeutics, vol. 301, no. 2, pp. 543–550, 2002. View at Publisher · View at Google Scholar · View at Scopus
  120. J. E. Packer, T. F. Slater, and R. L. Willson, “Direct observation of a free radical interaction between vitamin E and vitamin C,” Nature, vol. 278, no. 5706, pp. 737–738, 1979. View at Scopus
  121. E. Niki, N. Noguchi, H. Tsuchihashi, and N. Gotoh, “Interaction among vitamin C, vitamin E, and β-carotene,” American Journal of Clinical Nutrition, vol. 62, no. 6, 1995. View at Scopus
  122. J. M. May, Z.-C. Qu, and S. Mendiratta, “Protection and recycling of α-tocopherol in human erythrocytes by intracellular ascorbic acid,” Archives of Biochemistry and Biophysics, vol. 349, no. 2, pp. 281–289, 1998. View at Publisher · View at Google Scholar · View at Scopus
  123. J. M. Cárcamo, A. Pedraza, O. Bórquez-Ojeda, and D. W. Golde, “Vitamin C suppresses TNF alpha-induced NF kappa B activation by inhibiting I kappa B alpha phosphorylation,” Biochemistry, vol. 41, pp. 12995–13002, 2002.
  124. Z. Yang and X.-F. Ming, “Recent advances in understanding endothelial dysfunction in atherosclerosis,” Clinical Medicine and Research, vol. 4, no. 1, pp. 53–65, 2006. View at Publisher · View at Google Scholar · View at Scopus
  125. S. Taddei, A. Virdis, L. Ghiadoni, A. Magagna, and A. Salvetti, “Vitamin C improves endothelium-dependent vasodilation by restoring nitric oxide activity in essential hypertension,” Circulation, vol. 97, no. 22, pp. 2222–2229, 1998. View at Scopus
  126. H. H. Ting, F. K. Timimi, K. S. Boles, S. J. Creager, P. Ganz, and M. A. Creager, “Vitamin C improves endothelium-dependent vasodilation in patients with non-insulin-dependent diabetes mellitus,” Journal of Clinical Investigation, vol. 97, no. 1, pp. 22–28, 1996. View at Scopus
  127. S. Basili, G. Tanzilli, E. Mangieri et al., “Intravenous ascorbic acid infusion improves myocardial perfusion grade during elective percutaneous coronary intervention. Relationship with oxidative stress markers,” Cardiovascular Interventions, vol. 3, no. 2, pp. 221–229, 2010. View at Publisher · View at Google Scholar · View at Scopus
  128. P. Bhakuni, M. Chandra, and M. K. Misra, “Effect of ascorbic acid supplementation on certain oxidative stress parameters in the post reperfusion patients of myocardial infarction,” Molecular and Cellular Biochemistry, vol. 290, no. 1-2, pp. 153–158, 2006. View at Publisher · View at Google Scholar · View at Scopus
  129. C. A. Molyneux, M. C. Glyn, and B. J. Ward, “Oxidative stress and cardiac microvascular structure in ischemia and reperfusion: the protective effect of antioxidant vitamins,” Microvascular Research, vol. 64, no. 2, pp. 265–277, 2002. View at Publisher · View at Google Scholar · View at Scopus
  130. N. G. Stephens, A. Parsons, P. M. Schofield et al., “Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS),” The Lancet, vol. 347, no. 9004, pp. 781–786, 1996. View at Publisher · View at Google Scholar · View at Scopus
  131. J. M. Rapola, J. Virtamo, S. Ripatti et al., “Randomised trial of α-tocopherol and β-carotene supplements on incidence of major coronary events in men with previous myocardial infarction,” The Lancet, vol. 349, no. 9067, pp. 1715–1720, 1997. View at Publisher · View at Google Scholar · View at Scopus
  132. GISSI-Prevenzione trial, “Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico,” The Lancet, vol. 354, no. 9177, pp. 447–455, 1999.
  133. S. Yusuf, G. Dagenais, J. Pogue, J. Bosch, and P. Sleight, “Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators,” The New England Journal of Medicine, vol. 342, pp. 154–160, 2000.
  134. G. de Gaetano and Collaborative Group of the Primary Prevention Project, “Low-dose aspirin and vitamin E in people at cardiovascular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project,” The Lancet, vol. 357, pp. 89–95, 2001.
  135. R. Collins, J. Armitage, S. Parish, P. Sleight, and R. Peto, “MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial,” The Lancet, vol. 360, no. 9326, pp. 23–33, 2002. View at Publisher · View at Google Scholar · View at Scopus
  136. N. R. Cook, C. M. Albert, J. M. Gaziano et al., “A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the women's antioxidant cardiovascular study,” Archives of Internal Medicine, vol. 167, no. 15, pp. 1610–1618, 2007. View at Publisher · View at Google Scholar · View at Scopus
  137. H. D. Sesso, J. E. Buring, W. G. Christen et al., “Vitamins E and C in the prevention of cardiovascular disease in men: the physicians' health study II randomized controlled trial,” Journal of the American Medical Association, vol. 300, no. 18, pp. 2123–2133, 2008. View at Publisher · View at Google Scholar · View at Scopus
  138. A. M. Evans and G. Fornasini, “Pharmacokinetics of L-carnitine,” Clinical Pharmacokinetics, vol. 42, no. 11, pp. 941–967, 2003. View at Publisher · View at Google Scholar · View at Scopus
  139. E. I. Kalenikova, E. A. Gorodetskaya, and O. S. Medvedev, “Pharmacokinetics of coenzyme Q10,” Bulletin of Experimental Biology and Medicine, vol. 146, no. 3, pp. 313–316, 2008. View at Publisher · View at Google Scholar · View at Scopus
  140. R. Rodrigo, C. Guichard, and R. Charles, “Clinical pharmacology and therapeutic use of antioxidant vitamins,” Fundamental and Clinical Pharmacology, vol. 21, no. 2, pp. 111–127, 2007. View at Publisher · View at Google Scholar · View at Scopus
  141. A. C. Maritim, R. A. Sanders, and J. B. Watkins III, “Diabetes, oxidative stress, and antioxidants: a review,” Journal of Biochemical and Molecular Toxicology, vol. 17, no. 1, pp. 24–38, 2003. View at Publisher · View at Google Scholar · View at Scopus
  142. S. Cuzzocrea, D. P. Riley, A. P. Caputi, and D. Salvemini, “Antioxidant therapy: a new pharmacological approach in shock, inflammation, and ischemia/reperfusion injury,” Pharmacological Reviews, vol. 53, no. 1, pp. 135–159, 2001. View at Scopus
  143. V. Digiesi, M. Lenuzza, and G. Digiesi, “Prospects for the use of antioxidant therapy in hypertension,” Annali Italiani di Medicina Interna, vol. 16, no. 2, pp. 93–100, 2001. View at Scopus
  144. R. Gardner, A. Salvador, and P. Moradas-Ferreira, “Why does SOD overexpression sometimes enhance, sometimes decrease, hydrogen peroxide production? A minimalist explanation,” Free Radical Biology and Medicine, vol. 32, no. 12, pp. 1351–1357, 2002. View at Publisher · View at Google Scholar · View at Scopus
  145. I. Jialal, S. Devaraj, and N. Kaul, “The effect of α-Tocopherol on monocyte proatherogenic activity,” Journal of Nutrition, vol. 131, no. 2, pp. 389–394, 2001. View at Scopus