The breathing heart - Mitochondrial respiratory chain dysfunction in cardiac disease

International Journal of Cardiology

Volumn 171, Issue 2, 2014, Pages 134-143

  Schwarz, Konstantin ^a   Siddiqi, Nishat ^a   Singh, Satnam ^a   Neil, Christopher J ^a,b   Dawson, Dana K ^a   Frenneaux, Michael P ^a  

^a UNIVERSITY OF ABERDEEN   (United Kingdom)

^b WESTERN HEALTH   (Australia)

Author keywords

Heart; Mitochondria; Oxydative phosphorylation; Respiratory chain

Indexed keywords

ACETYLCYSTEINE; ADENOSINE; ADENOSINE TRIPHOSPHATE; ALPHA TOCOPHEROL; AMOBARBITAL; ANTIOXIDANT; ATRIAL NATRIURETIC FACTOR; CARDIOVASCULAR AGENT; CYCLOSPORIN A; HYDROGEN SULFIDE; MELATONIN; NITRATE; NITRITE; NORPHENAZONE; OMEGA 3 FATTY ACID; OPIATE; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; REACTIVE OXYGEN METABOLITE; RESVERATROL; SELENIUM; SS 31; TRIMETAZIDINE; TRO 40303; UBIDECARENONE; UNCLASSIFIED DRUG;

ACUTE HEART INFARCTION; AEROBIC EXERCISE; AGING; BARTH SYNDROME; CALORIC RESTRICTION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; HEART DISEASE; HEART FAILURE; HEART INFARCTION PREVENTION; HEART LEFT VENTRICLE HYPERTROPHY; HEART MUSCLE OXYGEN CONSUMPTION; HUMAN; MITOCHONDRIAL RESPIRATION; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REPERFUSION INJURY; REVIEW; ST SEGMENT ELEVATION MYOCARDIAL INFARCTION; THERAPY EFFECT; VENTRICULAR NONCOMPACTION;

HEART; MITOCHONDRIA; OXYDATIVE PHOSPHORYLATION; RESPIRATORY CHAIN;

ELECTRON TRANSPORT; HEART; HUMANS; MITOCHONDRIA; MITOCHONDRIAL DISEASES; MYOCARDIUM; OXIDATIVE PHOSPHORYLATION; OXYGEN CONSUMPTION;

EID: 84892880554     PISSN: 01675273     EISSN: 18741754     Source Type: Journal    
DOI: 10.1016/j.ijcard.2013.12.014     Document Type: Review

References (136)

1. S. Neubauer The failing heart - an engine out of fuel N Engl J Med 356 11 2007 1140 1151
2. A.J. Murray, R.E. Anderson, G.C. Watson, G.K. Radda, and K. Clarke Uncoupling proteins in human heart Lancet 364 9447 2004 1786 1788
3. R.J. Mailloux, and M.- Harper Uncoupling proteins and the control of mitochondrial reactive oxygen species production Free Radic Biol Med 51 6 2011 1106 1115
4. M.D. Brand Uncoupling to survive? The role of mitochondrial inefficiency in ageing Exp Gerontol 35 6-7 2000 811 820
5. S.L. Chan, Z. Wei, S. Chigurupati, and W. Tu Compromised respiratory adaptation and thermoregulation in aging and age-related diseases Ageing Res Rev 9 1 2010 20 40
6. M. Jastroch, A.S. Divakaruni, S. Mookerjee, J.R. Treberg, and M.D. Brand Mitochondrial proton and electron leaks Essays Biochem 47 2010 53 67
7. B.P. Dranka, G.A. Benavides, and A.R. Diers et al. Assessing bioenergetic function in response to oxidative stress by metabolic profiling Free Radic Biol Med 51 9 2011 1621 1635
8. D.C. Wallace A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine Annu Rev Genet 39 2005 359 407
9. E.A. Shoubridge Nuclear genetic defects of oxidative phosphorylation Hum Mol Genet 10 20 2001 2277 2284
10. A. Rötig Genetic bases of mitochondrial respiratory chain disorders Diabetes Metab 36 2 4 2010 97 107
11. C. Giordano, E. Perli, and M. Orlandi et al. Cardiomyopathies due to homoplasmic mitochondrial tRNA mutations: morphologic and molecular features Hum Pathol 44 7 7 2013 1262 1270
12. S. DiMauro, and E.A. Schon Mitochondrial respiratory-chain diseases N Engl J Med 348 26 2003 2656 2668
13. M.G.D. Bates, J.P. Bourke, C. Giordano, G. D'Amati, D.M. Turnbull, and R.W. Taylor Cardiac involvement in mitochondrial DNA disease: clinical spectrum, diagnosis, and management Eur Heart J 33 24 2012 3023 3033
14. S.B. Bleyl, B.R. Mumford, and V. Thompson et al. Neonatal, lethal noncompaction of the left ventricular myocardium is allelic with Barth syndrome Am J Hum Genet 61 4 1997 868 872
15. O. Leone, J.P. Veinot, and A. Angelini et al. 2011 consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology Cardiovasc Pathol 21 4 2012 245 274
16. D. Harman Free radical theory of aging Mutat Res DNAging Genet Instabil Aging 275 3-6 1992 257 266
17. K.R. Short, M.L. Bigelow, and J. Kahl et al. Decline in skeletal muscle mitochondrial function with aging in humans Proc Natl Acad Sci U S A 102 15 2005 5618 5623
18. C. Richter, J.- Park, and B.N. Ames Normal oxidative damage to mitochondrial and nuclear DNA is extensive Proc Natl Acad Sci U S A 85 17 1988 6465 6467
19. T.M. Hagen, R. Moreau, J.H. Suh, and F. Visioli Mitochondrial decay in the aging rat heart: evidence for improvement by dietary supplementation with acetyl-l-carnitine and/or lipoic acid Ann N Y Acad Sci 959 2002 491 507
20. K.R. Chaudhary, H. El-Sikhry, and J.M. Seubert Mitochondria and the aging heart J Geriatr Cardiol 8 3 2011 159 167
21. J. Sun, D. Folk, T.J. Bradley, and J. Tower Induced overexpression of mitochondrial Mn-superoxide dismutase extends the life span of adult Drosophila melanogaster Genetics 161 2 2002 661 672
22. S.E. Schriner, and N.J. Linford Extension of mouse lifespan by overexpression of catalase Age 28 2 2006 209 218
23. M. Nabben, J. Hoeks, and J.J. Briedé et al. The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice FEBS Lett 582 30 2008 4147 4152
24. J.R. Speakman, D.A. Talbot, and C. Selman et al. Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer Aging Cell 3 3 2004 87 95
25. F.M. Cerqueira, F.R.M. Laurindo, and A.J. Kowaltowski Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, Akt and mitochondrial biogenesis PLoS One 6 3 2011
26. A. Trifunovic, A. Hansson, and A. Wredenberg et al. Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production Proc Natl Acad Sci U S A 102 50 2005 17993 17998
27. A.M. Cuervo, E. Bergamini, U.T. Brunk, W. Dröge, M. Ffrench, and A. Terman Autophagy and aging: the importance of maintaining "clean" cells Autophagy 1 3 2005 131 140
28. M. Liesa, M. Palacín, and A. Zorzano Mitochondrial dynamics in mammalian health and disease Physiol Rev 89 3 2009 799 845
29. M. Taneike, O. Yamaguchi, and A. Nakai et al. Inhibition of autophagy in the heart induces age-related cardiomyopathy Autophagy 6 5 2010 600 606
30. F.J. Giordano Oxygen, oxidative stress, hypoxia, and heart failure J Clin Invest 115 3 2005 500 508
31. A. Sabri, H.H. Hughie, and P.A. Lucchesi Regulation of hypertrophic and apoptotic signaling pathways by reactive oxygen species in cardiac myocytes Antioxid Redox Signal 5 6 2003 731 740
32. M. Kindo, S. Gerelli, and J. Bouitbir et al. Pressure overload-induced mild cardiac hypertrophy reduces left ventricular transmural differences in mitochondrial respiratory chain activity and increases oxidative stress Front Physiol 3 Aug 2012
33. H. Tsutsui, S. Kinugawa, and S. Matsushima Oxidative stress and heart failure Am J Physiol Heart Circ Physiol 301 6 2011 2181 2190
34. E.R. Griffiths, I. Friehs, E. Scherr, D. Poutias, F.X. McGowan, and P.J. del Nido Electron transport chain dysfunction in neonatal pressure-overload hypertrophy precedes cardiomyocyte apoptosis independent of oxidative stress J Thorac Cardiovasc Surg 139 6 2010 1609 1617
35. V.G. Sharov, A. Goussev, M. Lesch, S. Goldstein, and H.N. Sabbah Abnormal mitochondrial function in myocardium of dogs with chronic heart failure J Mol Cell Cardiol 30 9 1998 1757 1762
36. V.G. Sharov, A.V. Todor, N. Silverman, S. Goldstein, and H.N. Sabbah Abnormal mitochondrial respiration in failed human myocardium J Mol Cell Cardiol 32 12 2000 2361 2367
37. X. Gao, J.L. Campian, M. Qian, X.- Sun, and J.W. Eaton Mitochondrial DNA damage in iron overload J Biol Chem 284 8 2009 4767 4775
38. X. Gao, M. Qian, and J.L. Campian et al. Mitochondrial dysfunction may explain the cardiomyopathy of chronic iron overload Free Radic Biol Med 49 3 2010 401 407
39. A. Báez, M.S.L. Presti, and H.W. Rivarola et al. Mitochondrial involvement in chronic chagasic cardiomyopathy Trans R Soc Trop Med Hyg 105 5 2011 239 246
40. R.J. Scheubel, M. Tostlebe, and A. Simm et al. Dysfunction of mitochondrial respiratory chain complex I in human failing myocardium is not due to disturbed mitochondrial gene expression J Am Coll Cardiol 40 12 2002 2174 2181
41. D. Jarreta, J. Orús, and A. Barrientos et al. Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy Cardiovasc Res 45 4 2000 860 865
42. E. Arbustini, M. Diegoli, and R. Fasani et al. Mitochondrial DNA mutations and mitochondrial abnormalities in dilated cardiomyopathy Am J Pathol 153 5 1998 1501 1510
43. T. Ide, H. Tsutsui, and S. Kinugawa et al. Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium Circ Res 85 4 1999 357 363
44. F. Sam, D.L. Kerstetter, and D.R. Pimental et al. Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium J Card Fail 11 6 2005 473 480
45. C. Maack, and M. Bhm Targeting mitochondrial oxidative stress in heart failure: throttling the afterburner J Am Coll Cardiol 58 1 2011 83 86
46. A.P. Halestrap, S.J. Clarke, and S.A. Javadov Mitochondrial permeability transition pore opening during myocardial reperfusion - a target for cardioprotection Cardiovasc Res 61 3 2004 372 385
47. J. Hokamaki, H. Kawano, and M. Yoshimura et al. Urinary biopyrrins levels are elevated in relation to severity of heart failure J Am Coll Cardiol 43 10 2004 1880 1885
48. D. Murillo, C. Kamga, L. Mo, and S. Shiva Nitrite as a mediator of ischemic preconditioning and cytoprotection Nitric Oxide Biol Chem 25 2 2011 70 80
49. A.P. Halestrap Mitochondria and reperfusion injury of the heart - a holey death but not beyond salvation J Bioenerg Biomembr 41 2 2009 113 121
50. E.J. Griffiths, and A.P. Halestrap Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion Biochem J 307 1 1995 93 98
51. Y.- Chen, C.- Chen, D.R. Pfeiffer, and J.L. Zweier Mitochondrial complex II in the post-ischemic heart: oxidative injury and the role of protein S-glutathionylation J Biol Chem 282 45 2007 32640 32654
52. L.B. Becker New concepts in reactive oxygen species and cardiovascular reperfusion physiology Cardiovasc Res 61 3 2004 461 470
53. B. O'Rourke, S. Cortassa, and M.A. Aon Mitochondrial ion channels: gatekeepers of life and death Physiology 20 5 2005 303 315
54. G. Ambrosio, J.L. Zweier, and C. Duilio et al. Evidence that mitochondrial respiration is a source of potentially toxic oxygen free radicals in intact rabbit hearts subjected to ischemia and reflow J Biol Chem 268 25 1993 18532 18541
55. E. Murphy, and C. Steenbergen Ion transport and energetics during cell death and protection Physiology 23 2 2008 115 123
56. N.G. Frangogiannis, C.W. Smith, and M.L. Entman The inflammatory response in myocardial infarction Cardiovasc Res 53 1 2002 31 47
57. R.K. Kharbanda Cardiac conditioning: a review of evolving strategies to reduce ischaemia-reperfusion injury Heart 96 15 2010 1179 1186
58. S. Javadov, M. Karmazyn, and N. Escobales Mitochondrial permeability transition pore opening as a promising therapeutic target in cardiac diseases J Pharmacol Exp Ther 330 3 2009 670 678
59. C. Piot, P. Croisille, and P. Staat et al. Effect of cyclosporine on reperfusion injury in acute myocardial infarction N Engl J Med 359 5 2008 473 481
60. K.G. Rajesh, S. Sasaguri, R. Suzuki, and H. Maeda Antioxidant MCI-186 inhibits mitochondrial permeability transition pore and upregulates Bcl-2 expression Am J Physiol Heart Circ Physiol 285 5 54-5 2003 H2171 H2178
61. S. Feng, Q. Yang, and M. Liu et al. Edaravone for acute ischaemic stroke Cochrane Database Syst Rev 12 2011 [Online]
62. K. Tsujita, H. Shimomura, and H. Kawano et al. Effects of edaravone on reperfusion injury in patients with acute myocardial infarction Am J Cardiol 94 4 2004 481 484
63. S. Schaller, S. Paradis, and G.A. Ngoh et al. TRO40303, a new cardioprotective compound, inhibits mitochondrial permeability transition J Pharmacol Exp Ther 333 3 2010 696 706
64. Safety and Efficacy Study of TRO40303 for Reduction of Reperfusion Injury in Patients Undergoing Percutaneous Coronary Intervention for Acute Myocardial Infarction Available at: http://clinicaltrials.gov/show/NCT01374321
65. D.J. Hausenloy, and D.M. Yellon New directions for protecting the heart against ischaemia-reperfusion injury: targeting the reperfusion injury salvage kinase (RISK)-pathway Cardiovasc Res 61 3 2004 448 460
66. L. Lacerda, S. Somers, L.H. Opie, and S. Lecour Ischaemic postconditioning protects against reperfusion injury via the SAFE pathway Cardiovasc Res 84 2 2009 201 208
67. T. Minamino Cardioprotection from ischemia/reperfusion injury: basic and translational research Circ J 76 5 2012 1074 1082
68. B. Ebner, A. Ebner, and A. Reetz et al. Pharmacological postconditioning by bolus injection of phosphodiesterase-5 inhibitors vardenafil and sildenafil Mol Cell Biochem 379 1-2 2013 43 49
69. J. Nagendran, T.J. Waller, and J.R.B. Dyck AMPK signalling and the control of substrate use in the heart Mol Cell Endocrinol 366 2 2013 180 193
70. M.R. Schmidt, M. Smerup, and I.E. Konstantinov et al. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a K ATP-dependent mechanism: first demonstration of remote ischemic perconditioning Am J Physiol Heart Circ Physiol 292 4 2007 H1883 H1890
71. H.E. Bøtker, R. Kharbanda, and M.R. Schmidt et al. Remote ischaemic conditioning before hospital admission, as a complement to angioplasty, and effect on myocardial salvage in patients with acute myocardial infarction: a randomised trial Lancet 375 9716 2010 727 734
72. L. Li, W. Luo, and L. Huang et al. Remote perconditioning reduces myocardial injury in adult valve replacement: a randomized controlled trial J Surg Res 164 1 2010 e21 e26
73. D.J. Hausenloy, P.K. Mwamure, and V. Venugopal et al. Effect of remote ischaemic preconditioning on myocardial injury in patients undergoing coronary artery bypass graft surgery: a randomised controlled trial Lancet 370 9587 2007 575 579
74. S.P. Hoole, P.M. Heck, and L. Sharples et al. Cardiac remote ischemic preconditioning in coronary stenting (CRISP stent) study. A prospective, randomized control trial Circulation 119 6 2009 820 827
75. M. Thielmann, E. Kottenberg, and P. Kleinbongard et al. Cardioprotective and prognostic effects of remote ischaemic preconditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial Lancet 382 9892 2013 597 604
76. + leak and ROS generation: an odd couple Free Radic Biol Med 38 1 1/1 2005 12 23
77. S.M. Nadtochiy, A.J. Tompkins, and P.S. Brookes Different mechanisms of mitochondrial proton leak in ischaemia/reperfusion injury and preconditioning: implications for pathology and cardioprotection Biochem J 395 3 2006 611 618
78. J.A. Cabrera, E.A. Ziemba, and R. Colbert et al. Altered expression of mitochondrial electron transport chain proteins and improved myocardial energetic state during late ischemic preconditioning Am J Physiol Heart Circ Physiol 302 10 2012 H1974 H1982
79. L.S. Burwell, S.M. Nadtochiy, A.J. Tompkins, S. Young, and P.S. Brookes Direct evidence for S-nitrosation of mitochondrial complex I Biochem J 394 3 2006 627 634
80. J.O. Lundberg, E. Weitzberg, and M.T. Gladwin The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics Nat Rev Drug Discov 7 2 2008 156 167
81. J.L. Zweier, H. Li, A. Samouilov, and X. Liu Mechanisms of nitrite reduction to nitric oxide in the heart and vessel wall Nitric Oxide Biol Chem 22 2 2010 83 90
82. S.M. Nadtochiy, L.S. Burwell, and P.S. Brookes Cardioprotection and mitochondrial S-nitrosation: effects of S-nitroso-2-mercaptopropionyl glycine (SNO-MPG) in cardiac ischemia-reperfusion injury J Mol Cell Cardiol 42 4 2007 812 825
83. C.E. Cooper, and G.C. Brown The inhibition of mitochondrial cytochrome oxidase by the gases carbon monoxide, nitric oxide, hydrogen cyanide and hydrogen sulfide: chemical mechanism and physiological significance J Bioenerg Biomembr 40 5 2008 533 539
84. E.J. Murphy, C.L. Metcalfe, J. Basran, P.C.E. Moody, and E.L. Raven Engineering the substrate specificity and reactivity of a heme protein: creation of an ascorbate binding site in cytochrome c peroxidase Biochemistry (N Y) 47 52 2008 13933 13941
85. S.M. Nadtochiy, L.S. Burwell, and C.A. Ingraham et al. In vivo cardioprotection by S-nitroso-2-mercaptopropionyl glycine J Mol Cell Cardiol 46 6 2009 960 968
86. S. Shiva, M.N. Sack, and J.J. Greer et al. Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer J Exp Med 204 9 2007 2089 2102
87. NIAMI http://clinicaltrials.gov/ct2/show/NCT01388504
88. Safety and effectiveness of intra-coronary nitrite in acute myocardial infarction (NITRITE-AMI) http://clinicaltrials.gov/show/NCT01584453
89. Q. Chen, M. Paillard, L. Gomez, H. Li, Y. Hu, and E.J. Lesnefsky Postconditioning modulates ischemia-damaged mitochondria during reperfusion J Cardiovasc Pharmacol 59 1 2012 101 108
90. S. Stewart, E.J. Lesnefsky, and Q. Chen Reversible blockade of electron transport with amobarbital at the onset of reperfusion attenuates cardiac injury Transl Res 153 5 2009 224 231
91. Q. Chen, A.K.S. Camara, D.F. Stowe, C.L. Hoppel, and E.J. Lesnefsky Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion Am J Physiol Cell Physiol 292 1 2007 C137 C147
92. Q. Chen, T. Ross, Y. Hu, and E.J. Lesnefsky Blockade of electron transport at the onset of reperfusion decreases cardiac injury in aged hearts by protecting the inner mitochondrial membrane J Aging Res 2012 2012
93. A.M. Walters, G.A. Porter, and P.S. Brookes Mitochondria as a drug target in ischemic heart disease and cardiomyopathy Circ Res 111 9 2012 1222 1236
94. A.A. Kenjale, K.L. Ham, and T. Stabler et al. Dietary nitrate supplementation enhances exercise performance in peripheral arterial disease J Appl Physiol 110 6 2011 1582 1591
95. P. Clerc, M. Rigoulet, X. Leverve, and E. Fontaine Nitric oxide increases oxidative phosphorylation efficiency J Bioenerg Biomembr 39 2 2007 158 166
96. 2 cost of low-intensity exercise and enhances tolerance to high-intensity exercise in humans J Appl Physiol 107 4 2009 1144 1155
97. F.J. Larsen, E. Weitzberg, J.O. Lundberg, and B. Ekblom Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise Free Radic Biol Med 48 2 2010 342 347
98. F.J. Larsen, T.A. Schiffer, and S. Borniquel et al. Dietary inorganic nitrate improves mitochondrial efficiency in humans Cell Metab 13 2 2011 149 159
99. A.R. Maher, A.B. Milsom, and P. Gunaruwan et al. Hypoxic modulation of exogenous nitrite-induced vasodilation in humans Circulation 117 5 2008 670 677
100. D. Kumar, B.G. Branch, and C.B. Pattillo et al. Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis Proc Natl Acad Sci U S A 105 21 2008 7540 7545
101. U.B. Hendgen-Cotta, P. Luedike, and M. Totzeck et al. Dietary nitrate supplementation improves revascularization in chronic ischemia Circulation 126 16 2012 1983 1992
102. S.L. Molyneux, C.M. Florkowski, and P.M. George et al. Coenzyme Q 10. An independent predictor of mortality in chronic heart failure J Am Coll Cardiol 52 18 2008 1435 1441
103. U. Alehagen, P. Johansson, M. Björnstedt, A. Rosén, and U. Dahlström Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens Int J Cardiol 167 5 2013 1860 1866
104. Q-Symbio http://isrctn.org/ISRCTN94506234
105. S.A. Mortensen, A. Kumar, and P. Dolliner et al. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure. Results from the Q-SYMBIO study Presented at Heart Failure Congress 2013 final programme number 440 Coenzyme Q10 as adjunctive treatment of chronic heart failure: a randomised double blind multicentre trial with focus on changes in symptoms, biomarker status with BNP and long term outcome 25th May 2013
106. V. Valls-Belles, C. Torres, P. Muñiz, and P. Codoñer-Franch Effect of beer consumption on levels of complex I and complex IV liver and heart mitochondrial enzymes and coenzymes Q9 and Q10 in adriamycin-treated rats Eur J Nutr 49 3 2010 181 187
107. G. Paradies, G. Petrosillo, V. Paradies, R.J. Reiter, and F.M. Ruggiero Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease J Pineal Res 48 4 2010 297 310
108. MARIA trial Available at: http://clinicaltrials.gov/ct2/show/NCT00640094
109. M.I. Rodríguez, M. Carretero, and G. Escames et al. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice Free Radic Res 41 1 2007 15 24
110. C. Vitale, M. Wajngaten, and B. Sposato et al. Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease Eur Heart J 25 20 2004 1814 1821
111. H. Tuunanen, E. Engblom, and A. Naum et al. Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy Circulation 118 12 2008 1250 1258
112. G. Fragasso, G. Perseghin, and F. De Cobelli et al. Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure Eur Heart J 27 8 2006 942 948
113. G. Fragasso, A. Salerno, and G. Lattuada et al. Effect of partial inhibition of fatty acid oxidation by trimetazidine on whole body energy metabolism in patients with chronic heart failure Heart 97 18 2011 1495 1500
114. H. Ashrafian, M.P. Frenneaux, and L.H. Opie Metabolic mechanisms in heart failure Circulation 116 4 2007 434 448
115. P.F. Kantor, A. Lucien, R. Kozak, and G.D. Lopaschuk The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase Circ Res 86 5 2000 580 588
116. L. Argaud, L. Gomez, and O. Gateau-Roesch et al. Trimetazidine inhibits mitochondrial permeability transition pore opening and prevents lethal ischemia-reperfusion injury J Mol Cell Cardiol 39 6 2005 893 899
117. E.N. Dedkova, L.K. Seidlmayer, and L.A. Blatter Mitochondria-mediated cardioprotection by trimetazidine in rabbit heart failure J Mol Cell Cardiol 59 2013 41 54
118. N. Naidoo, R.B. van Dam, and W.- Koh et al. Plasma vitamin E and coenzyme Q10 are not associated with a lower risk of acute myocardial infarction in Singapore Chinese adults J Nutr 142 6 2012 1046 1052
119. P.G. Shekelle, S.C. Morton, and L.K. Jungvig et al. Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease J Gen Intern Med 19 4 2004 380 389
120. S.M. Kwak, S.- Myung, Y.J. Lee, and H.G. Seo Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials Arch Intern Med 172 9 2012 686 694
121. M. Bayeva, M. Gheorghiade, and H. Ardehali Mitochondria as a therapeutic target in heart failure J Am Coll Cardiol 61 6 2013 599 610
122. D.- Dai, T. Chen, and H. Szeto et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy J Am Coll Cardiol 58 1 2011 73 82
123. G. Barja Aging in vertebrates, and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism? Biol Rev Camb Philos Soc 79 2 2004 235 251
124. L.M. Redman, and E. Ravussin Caloric restriction in humans: Impact on physiological, psychological, and behavioral outcomes Antioxid Redox Signal 14 2 2011 275 287
125. R.A. Gottlieb, and R.M. Mentzer Autophagy during cardiac stress: Joys and frustrations of autophagy Annu Rev Physiol 72 2010 45 59
126. R. Gredilla, A. Sanz, M. Lopez-Torres, and G. Barja Caloric restriction decreases mitochondrial free radical generation at complex I and lowers oxidative damage to mitochondrial DNA in the rat heart FASEB J 15 9 2001 1589 1591
127. T.E. Meyer, S.J. Kovács, A.A. Ehsani, S. Klein, J.O. Holloszy, and L. Fontana Long-term caloric restriction ameliorates the decline in diastolic function in humans J Am Coll Cardiol 47 2 2006 398 402
128. K. Shinmura, K. Tamaki, and M. Sano et al. Caloric restriction primes mitochondria for ischemic stress by deacetylating specific mitochondrial proteins of the electron transport chain Circ Res 109 4 2011 396 406
129. C.A. Emter, and C.P. Baines Low-intensity aerobic interval training attenuates pathological left ventricular remodeling and mitochondrial dysfunction in aortic-banded miniature swine Am J Physiol Heart Circ Physiol 299 5 2010 H1348 H1356
130. S. Guo, A. Olm-Shipman, and A. Walters et al. A cell-based phenotypic assay to identify cardioprotective agents Circ Res 110 7 2012 948 957
131. V.M. Gohil, S.A. Sheth, and R. Nilsson et al. Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis Nat Biotechnol 28 3 2010 249 255
132. M.D. Brand, and D.G. Nicholls Assessing mitochondrial dysfunction in cells Biochem J 435 2 2011 297 312
133. D.J. Lefer, and R. Bolli Development of an NIH consortium for PreclinicAl AssESsment of CARdioprotective Therapies (CAESAR): a paradigm shift in studies of infarct size limitation J Cardiovasc Pharmacol Ther 16 3-4 2011 332 339
134. Q. Chen, and E.J. Lesnefsky Blockade of electron transport during ischemia preserves bcl-2 and inhibits opening of the mitochondrial permeability transition pore FEBS Lett 585 6 2011 921 926
135. J.W. Elrod, J.W. Calvert, and J. Morrison et al. Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function Proc Natl Acad Sci U S A 104 39 2007 15560 15565
136. S. Koene, and J. Smeitink Mitochondrial medicine: entering the era of treatment J Intern Med 265 2 2009 193 209