Heart failure and mitochondrial dysfunction: The role of mitochondrial fission/fusion abnormalities and new therapeutic strategies

Journal of Cardiovascular Pharmacology

Volumn 63, Issue 3, 2014, Pages 196-206

  Knowlton, Anne A ^a,b,c   Chen, Le ^a   Malik, Zulfiqar A ^a,b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

ACE inhibitor; Cardiovascular; Heart; Metformin; Mitochondria; Mitochondrial fission; Mitochondrial fusion; Ss 31

Indexed keywords

ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CATALASE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; METFORMIN; MITOCHONDRIAL PROTEIN; MITOFUSIN 1; MITOFUSIN 2; PEROXIDE; REACTIVE OXYGEN METABOLITE; SPIRONOLACTONE; UBIQUINONE;

BIOGENESIS; CARDIOMYOPATHY; CELL FUSION; CELL RESPIRATION; CELLULAR PARAMETERS; DIABETIC CARDIOMYOPATHY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG TARGETING; ENERGY TRANSFER; HEART FAILURE; HUMAN; INHIBITION KINETICS; ISCHEMIC HEART DISEASE; MITOCHONDRION; NEUROPATHY; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW;

ANIMALS; DRUG DESIGN; HEART FAILURE; HUMANS; MITOCHONDRIA, HEART; MITOCHONDRIAL DYNAMICS; MOLECULAR TARGETED THERAPY; MYOCYTES, CARDIAC; REACTIVE OXYGEN SPECIES;

EID: 84896316994     PISSN: 01602446     EISSN: 15334023     Source Type: Journal    
DOI: 10.1097/01.fjc.0000432861.55968.a6     Document Type: Review

References (131)

1. Margulis L. Symbiosis in Cell Evolution. New York, NY: W.H. Freeman; 1992
2. Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and mitochondrial DNA damage in heart failure. Circ J. 2008;72:A31-A37
3. Tsutsui H, Ide T, Hayashidani S, et al. Enhanced generation of reactive oxygen species in the Limb skeletal muscles from a murine infarct model of heart failure. Circulation. 2001;1042:134-136
4. Ide T, Tsutsui H, Kinugawa S, et al. Amiodarone protects cardiac myocytes against oxidative injury by its free radical scavenging action. Circulation. 1999;100:690-692
5. Belch JJ, Bridges AB, Scott N, et al. Oxygen free radicals and congestive heart failure. Br Heart J. 1991;65:245-248
6. Ide T, Tsutsui H, Kinugawa S, et al. Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium. Circ Res. 2000;86:152-157
7. Ide T, Tsutsui H, Kinugawa S, et al. Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium. Circ Res. 1999;85:357-363
8. Brown GC, Borutaite V. There is no evidence that mitochondria are the main source of reactive oxygen species in mammalian cells. Mitochondrion. 2012;12:1-4
9. Schulze-Osthoff K, Bakker AC, Vanhaesebroeck B, et al. Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions. Evidence for the involvement of mitochondrial radical generation. J Biol Chem. 1992;267:5317-5323
10. Zell R, Geck P, Werdan K, et al. TNF-alpha and IL-1 alpha inhibit both pyruvate dehydrogenase activity and mitochondrial function in cardiomyocytes: Evidence for primary impairment of mitochondrial function. Mol Cell Biochem. 1997;177:61-67
11. Lesnefsky EJ, Chen Q, Moghaddas S, et al. Blockade of electron transport during ischemia protects cardiac mitochondria. J Biol Chem. 2004; 279:47961-47967
12. Sirker A, Zhang M, Shah A. NADPH oxidases in cardiovascular disease: Insights from in vivo models and clinical studies. Basic Res Cardiol. 2011;106:735-747
13. Lambeth JD. NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol. 2004;4:181-189
14. Heymes C, Bendall JK, Ratajczak P, et al. Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol. 2003;41:2164-2171
15. Ago T, Kuroda J, Pain J, et al. Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res. 2010;106:1253-1264
16. Kuroda J, Ago T, Matsushima S, et al. NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA. 2010;107:15565-15570
17. Tsutsui H, Ide T, Hayashidani S, et al. Greater susceptibility of failing cardiac myocytes to oxygen free radical-mediated injury. Cardiovasc Res. 2001;49:103-109
18. Nojiri H, Shimizu T, Funakoshi M, et al. Oxidative stress causes heart failure with impaired mitochondrial respiration. J Biol Chem. 2006;281: 33789-33801
19. Siwik DA, Tzortzis JD, Pimental DR, et al. Inhibition of copper-zinc superoxide dismutase induces cell growth, hypertrophic phenotype, and apoptosis in neonatal rat cardiac myocytes in vitro. Circ Res. 1999;85: 147-153
20. Green DR, Reed JC. Mitochondria and apoptosis. Science. 1998;281: 1309-1313
21. Yang H, Brosel S, Acin-Perez R, et al. Analysis of mouse models of cytochrome c oxidase deficiency owing to mutations in Sco2. Hum Mol Genet. 2010;19:170-180
22. Weiss H, Wester-Rosenloef L, Koch C, et al. The mitochondrial Atp8 mutation induces mitochondrial ROS generation, secretory dysfunction, and b-cell mass adaptation in conplastic B6-mtFVB mice. Endocrinology. 2012;153:4666-4676
23. Jonckheere AI, Hogeveen M, Nijtmans LGJ, et al. A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy. J Med Genet. 2008;45:129-133
24. Kao HJ, Cheng CF, Chen YH, et al. ENU mutagenesis identifies mice with cardiac fibrosis and hepatic steatosis caused by a mutation in the mitochondrial trifunctional protein beta-subunit. Hum Mol Genet. 2006; 15:3569-3577
25. Graham BH, Waymire KG, Cottrell B, et al. A mouse model for mitochondrial myopathy and cardiomyopathy resulting from a deficiency in the heart/muscle isoform of the adenine nucleotide translocator. Nat Genet. 1997;16:226-234
26. Koyama H, Nojiri H, Kawakami S, et al. Antioxidants improve the phenotypes of dilated cardiomyopathy and muscle fatigue in mitochondrial superoxide dismutase-deficient mice. Molecules. 2013;18: 1383-1393
27. Chen Y, Liu Y, Dorn GW II. Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ Res. 2011;109: 1327-1331
28. Chen L, Liu TT, Tran AL, et al. OPA1 mutation and late onset cardiomyopathy: Mitochondrial dysfunction and mtDNA instability. J Am Heart Assoc. 2012;1:e003012
29. Ke BX, Pepe S, Grubb DR, et al. Tissue-specific splicing of an Ndufs6 gene-trap insertion generates a mitochondrial complex I deficiency-specific cardiomyopathy. Proc Natl Acad Sci USA. 2012;109:6165-6170
30. Ichikawa Y, Bayeva M, Ghanefar M, et al. Disruption of ATP-binding cassette B8 in mice leads to cardiomyopathy through a decrease in mitochondrial iron export. Proc Natl Acad Sci USA. 2012;109: 4152-4157
31. Horstkotte J, Perisic T, Schneider M, et al. Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection. Circulation. 2011;124:2892-2902
32. Acehan D, Vaz F, Houtkooper RH, et al. Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem. 2011;286:899-908
33. Wang J, Wilhelmsson H, Graff C, et al. Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mitochondrial DNA gene expression. Nat Genet. 1999;21: 133-137
34. Puccio H, Simon D, Cossee M, et al. Mouse models for Friedreich ataxia exhibit cardiomyopathy, sensory nerve defect and Fe-S enzyme deficiency followed by intramitochondrial iron deposits. Nat Genet. 2001;27:181-186
35. Shaw JM, Nunnari J. Mitochondrial dynamics and division in budding yeast. Trends Cell Biol. 2002;12:178-184
36. Chen H, Vermulst M, Wang YE, et al. Mitochondrial fusion is required for mtDNA stability in skeletal muscle and tolerance of mtDNA mutations. Cell. 2010;141:280-289
37. Chan DC. Mitochondria: Dynamic organelles in disease, aging and development. Cell. 2006;125:1241-1252
38. Liesa M, Palacin M, Zorzano A. Mitochondrial dynamics in mammalian health and disease. Physiol Rev. 2009;89:799-845
39. Legros F, Lombes A, Frachon P, et al. Mitochondrial fusion in human cells is efficient, requires the inner membrane potential, and is mediated by mitofusins. Mol Biol Cell. 2002;13:4343-4354
40. Chen K, Guo X, Ma D, et al. Dysregulation of HSG triggers vascular proliferative disorders. Nat Cell Biol. 2004;6:872-883
41. Bach D, Naon D, Pich S, et al. Expression of Mfn2, the Charcot-Marie- Tooth neuropathy type 2A gene, in human skeletal muscle. Diabetes. 2005;54:2685-2693
42. Gibala MJ, Little JP, MacDonald MJ, et al. Physiological adaptations to low-volume, high-intensity interval training in health and disease. J Physiol. 2012;590:1077-1084
43. Zorzano A, Liesa M, Sebastian D, et al. Mitochondrial fusion proteins: Dual regulators of morphology and metabolism. Semin Cell Dev Biol. 2010;21:566-574
44. Bras M, Yuste VJ, Roúe G, et al. Drp1 mediates caspase-independent type III cell death in normal and leukemic cells. Mol Cell Biol. 2007;27: 7073-7088
45. Cassidy-Stone A, Chipuk JE, Ingerman E, et al. Chemical inhibition of the mitochondrial division dynamin reveals its role in Bax/Bak-dependent mitochondrial outer membrane permeabilization. Dev Cell. 2008;14: 193-204
46. Lee Y, Jeong S, Karbowski M, et al. Roles of mammalian mitochondrial fission and fusion mediators Fis1, Drp1 and OPA1 in apoptosis. Mol Biol Cell. 2004;15:5001-5011
47. Merkwirth C, Dargazanli S, Tatsuta T, et al. Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes Dev. 2008;22:476-488
48. ElAchouri G, Vidoni S, Zanna C, et al. OPA1 links human mitochondrial genome maintenance to mtDNA replication. Genome Res. 2011; 21:12-20
49. Frezza C, Cipolat S, Martins de Brito O, et al. OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell. 2006;126:177-189
50. Yoon Y, Krueger EW, Oswald BJ, et al. The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol. 2003; 23:5409-5420
51. Smirnova E, Griparic L, Shurland DL, et al. Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells. Mol Biol Cell. 2001;12:2245-2256
52. Suzuki M, Jeong SY, Karbowski M, et al. The solution structure of human mitochondria fission protein Fis1 reveals a novel TPR-like helix bundle. J Mol Biol. 2003;334:445-458
53. Loson OC, Song Z, Chen H, et al. Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission. Mol Biol Cell. 2013;24:659-667
54. Palmer CS, Osellame LD, Laine D, et al. MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep. 2011;12:565-573
55. Gandre-Babbe S, Van Der Bliek AM. The novel tail-anchored membrane protein Mff Controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell. 2008;19:2402-2412
56. Zanna C, Ghelli A, Porcelli AM, et al. OPA1 mutations associated with dominant optic atrophy impair oxidative phosphorylation and mitochondrial fusion. Brain. 2008;131:352-367
57. Pollak MN. Investigating metformin for cancer prevention and treatment: The end of the beginning. Cancer Discov. 2012;2:778-790
58. Bhamra G, Hausenloy D, Davidson S, et al. Metformin protects the ischemic heart by the Akt-mediated inhibition of mitochondrial permeability transition pore opening. Basic Res Cardiol. 2008;103:274-284
59. Chen H, Chomyn A, Chan DC. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem. 2005;280: 26185-26192
60. Mayorov VI, Lowrey AJ, Biousse V, et al. Mitochondrial oxidative phosphorylation in autosomal dominant optic atrophy. BMC Biochem. 2008;9:22
61. Benard G, Bellance N, James D, et al. Mitochondrial bioenergetics and structural network organization. J Cell Sci. 2007;120:838-848
62. Twig G, Elorza A, Molina AJA, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433-446
63. Yu T, Sheu SS, Robotham JL, et al. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res. 2008;79:341-351
64. Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci USA. 2006;103:2653-2658
65. Amiott EA, Lott P, Soto J, et al. Mitochondrial fusion and function in Charcot-Marie-Tooth type 2A patient fibroblasts with mitofusin 2 mutations. Exp Neurol. 2008;211:115-127
66. Detmer SA, Chan DC. Complementation between mouse Mfn1 and Mfn2 protects mitochondrial fusion defects caused by CMT2A disease mutations. J Cell Biol. 2007;176:405-414
67. Hernandez-Alvarez MI, Thabit H, Burns N, et al. Subjects with earlyonset type 2 diabetes show defective activation of the skeletal muscle PGC-1a/Mitofusin-2 regulatory pathway in response to physical activity. Diabetes Care. 2010;33:645-651
68. Chen L, Gong Q, Stice JP, et al. Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res. 2009;84:91-99
69. Ong S, Hausenloy DJ. Mitochondrial morphology and cardiovascular disease. Cardiovasc Res. 2010;88:16-29
70. Ong S, Subrayan S, Lim SY, et al. Inhibiting mitochondrial fission protects the heart against ischemia/reperfusion injury. Circulation. 2010;121:2012-2022
71. Martinou JC, Youle RJ. Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 2011;21:92-101
72. Hom J, Yu T, Yoon Y, et al. Regulation of mitochondrial fission by intracellular Ca2+ in rat ventricular myocytes. Biochim Biophys Acta. 2010;1797:913-921
73. Kane L, Youle R. Mitochondrial fission and fusion and their roles in the heart. J Mol Med (Berl). 2010;88:971-979
74. Dorn GW II, Clark CF, Eschenbacher WH, et al Mitochondrial and cardiac function in Drosophila. Circ Res. 2011;108:12-17
75. Lukyanenko V, Chikando A, Lederer WJ. Mitochondria in cardiomyocyte Ca2+ signaling. Int J Biochem Cell Biol. 2009;41:1957-1971
76. Darshi M, Mendiola VL, Mackey MR, et al. ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J Biol Chem. 2011;286:2918-2932
77. Javadov S, Rajapurohitam V, Killic A, et al. Expression of mitochondrial fusion-fission proteins during post-infarction remodeling: The effect of NHE-1 inhibition. Basic Res Cardiol. 2011;106:99-109
78. Papanicolaou KN, Khairallah RJ, Ngoh GA, et al. Mitofusin-2 maintains mitochondrial structure and contributes to stress-induced permeability transition in cardiac myocytes. Mol Cell Biol. 2011;31:1309-1328
79. Davies V, Hollins A, Piechota M, et al. Opa1 deficiency in a mouse model of autosomal dominant optic atrophy impairs mitochondrial morphology, optic nerve structure and visual function. Hum Mol Genet. 2007;16:1307-1318
80. Karamanlidis G, Nascimben L, Couper GS, et al. Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res. 2010;106:1541-1548
81. Borchi E, Bargelli V, Stillitano F, et al. Enhanced ROS production by NADPH oxidase is correlated to changes in antioxidant enzyme activity in human heart failure. Biochim Biophys Acta. 2010;1802:331-338
82. Sam F, Kerstetter DL, Pimental DR, et al. Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium. J Card Fail. 2005;11:473-480
83. Ahuja P, Wanagat J, Wang Z, et al. Divergent mitochondrial biogenesis responses in human cardiomyopathy. Circulation. 2013;127:1957-1967
84. Garnier A, Zoll J, Fortin D, et al. Control by circulating factors of mitochondrial function and transcription cascade in heart failure/clinical perspective. Circ Heart Fail. 2009;2:342-350
85. Maejima Y, Kuroda J, Matsushima S, et al. Regulation of myocardial growth and death by NADPH oxidase. J Mol Cell Cardiol. 2011;50:408-416
86. Kim M, Shen M, Ngoy S, et al. AMPK isoform expression in the normal and failing hearts. J Mol Cell Cardiol. 2012;52:1066-1073
87. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: The central role of PGC-1a. Cardiovasc Res. 2008;79:208-217
88. Sihag S, Cresci S, Li AY, et al. PGC-1a and ERRa target gene downregulation is a signature of the failing human heart. J Mol Cell Cardiol. 2009;46:201-212
89. Hu X, Xu X, Lu Z, et al. Amp activated protein kinase-a2 regulates expression of estrogen-related receptor-a, a metabolic transcription factor related to heart failure development. Hypertension. 2011;58:696-703
90. Mirebeau-Prunier D, Le Pennec S, Jacques C, et al. Estrogen-related receptor a and PGC-1-related coactivator constitute a novel complex mediating the biogenesis of functional mitochondria. FEBS J. 2010; 277:713-725
91. Karamanlidis G, Bautista-Hernandez V, Fynn-Thompson F, et al. Impaired mitochondrial biogenesis precedes heart failure in right ventricular hypertrophy in congenital heart disease. Circ Heart Fail. 2011;4:707-713
92. Toga W, Tanonaka K, Takeo S. Changes in Hsp60 level of the failing heart following acute myocardial infarction and the effect of long-term treatment with trandolapril. Biol Pharm Bull. 2007;30:105-110
93. Momken I, Kahapip J, Bahi L, et al. Does angiotensin-converting enzyme inhibition improve the energetic status of cardiac and skeletal muscles in heart failure induced by aortic stenosis in rats? J Mol Cell Cardiol. 2003;35:399-407
94. Feng X, Luo Z, Ma L, et al. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-d/AMPK pathway. J Cell Mol Med. 2011;15:1572-1581
95. Andersson DC, Fauconnier J, Yamada T, et al. Mitochondrial production of reactive oxygen species contributes to the b-adrenergic stimulation of mouse cardiomyocytes. J Physiol. 2011;589:1791-1801
96. Kametani R, Miura T, Harada N, et al. Carvedilol inhibits mitochondrial oxygen consumption and superoxide production during calcium overload in isolated heart mitochondria. Circ J. 2006;70:321-326
97. Mulder P, Mellin V, Favre J, et al. Aldosterone synthase inhibition improves cardiovascular function and structure in rats with heart failure: A comparison with spironolactone. Eur Heart J. 2008;29:2171-2179
98. Bauersachs J, Hecker M, Fraccarollo D, et al. Addition of spironolactone to angiotensin-converting enzyme inhibition in heart failure improves endothelial vasomotor dysfunction: Role of vascular superoxide anion formation and endothelial nitric oxide synthase expression. J Am Coll Cardiol. 2002;39:351-358
99. Noda K, Kobara M, Hamada J, et al. Additive amelioration of oxidative stress and cardiac function by combined mineralocorticoid and angiotensin receptor blockers in postinfarct failing hearts. J Cardiovasc Pharmacol. 2012;60:140-149
100. Khurana R, Malik IS. Metformin: Safety in cardiac patients. Heart. 2010;96:99-102
101. Hirsch HA, Iliopoulos D, Struhl K. Metformin inhibits the inflammatory response associated with cellular transformation and cancer stem cell growth. Proc Natl Acad Sci USA. 2013;110:972-977
102. Masoudi FA, Inzucchi SE, Wang Y, et al. Thiazolidinediones, metformin, and outcomes in older patients with diabetes and heart failure: An observational study. Circulation. 2005;111:583-590
103. Aguilar D, Chan W, Bozkurt B, et al. Metformin use and mortality in ambulatory patients with diabetes and heart failure. Circ Heart Fail. 2011;4:53-58
104. Xie Z, Lau K, Eby B, et al. Improvement of cardiac functions by chronic metformin treatment is associated with enhanced cardiac autophagy in diabetic OVE26 mice. Diabetes. 2011;60:1770-1778
105. Gundewar S, Calvert JW, Jha S, et al. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res. 2009;104:403-411
106. Yin M, Van Der Horst ICC, van Melle JP, et al. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure. Am J Physiol Heart Circ Physiol. 2011;301:H459-H468
107. Benes J, Kazdova L, Drahota Z, et al. Effect of metformin therapy on cardiac function and survival in a volume-overload model of heart failure in rats. Clin Sci (Lond). 2011;121:29-41
108. Quentin T, Steinmetz M, Poppe A, et al. Metformin differentially activates ER stress signaling pathways without inducing apoptosis. Dis Model Mech. 2012;5:259-269
109. Shore DE, Carr CE, Ruvkun G. Induction of cytoprotective pathways is central to the extension of lifespan conferred by multiple longevity pathways. PLoS Genet. 2012;8:e1002792
110. Chen L, Knowlton AA. Mitochondrial dynamics in heart failure. Congest Heart Fail. 2011;17:257-261
111. Wang JX, Jiao JQ, Li Q, et al. miR-499 regulates mitochondrial dynamics by targeting calcineurin and dynamin-related protein-1. Nat Med. 2011;17:71-78
112. Takahashi R, Ikeda T, Hamaguchi A, et al. Coenzyme Q10 therapy in hereditary motor sensory neuropathy type VI with novel mitofusin 2 mutation. Intern Med. 2012;51:791-793
113. Fotino AD, Thompson-Paul AM, Bazzano LA. Effect of coenzyme Q10 supplementation on heart failure: A meta-analysis. Am J Clin Nutr. 2013; 97:268-275
114. Pich S, Bach D, Briones P, et al. The Charcot Marie Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 2005;14:1405-1415
115. Singh U, Devaraj S, Jialal I. Coenzyme Q10 supplementation and heart failure. Nutr Rev. 2007;65:286-293
116. Bayeva M, Gheorghiade M, Ardehali H. Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol. 2013;61:599-610
117. Rosca MG, Hoppel CL. New aspects of impaired mitochondrial function in heart failure. J Bioenerg Biomembr. 2009;41:107-112
118. Ide T, Tsutsui H, Hayashidani S, et al. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res. 2001;88:529-535
119. Tsutsui H, Kinugawa S, Matsushima S. Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res. 2009;81: 449-456
120. Ahmed Z, Tang WHW. Pharmacologic strategies to target oxidative stress in heart failure. Curr Heart Fail Rep. 2012;9:14-22
121. Keith ME, Jeejeebhoy KN, Langer A, et al. A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. Am J Clin Nutr. 2001;73:219-224
122. Kang YJ, Chen Y, Epstein PN. Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J Biol Chem. 1996;271:12610-12616
123. Li G, Chen Y, Saari JT, et al. Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury. Am J Physiol. 1997; 273:H1090-H1095
124. Schriner SE, Linford NJ, Martin GM, et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science. 2005;308:1909-1911
125. Dai DF, Johnson SC, Villarin JJ, et al. Mitochondrial oxidative stress mediates angiotensin II induced cardiac hypertrophy and Gaq overexpression induced heart failure. Circ Res. 2011;108:837-846
126. Zhao K, Zhao GM, Wu D, et al. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279: 34682-34690
127. Szeto H. Mitochondria-targeted peptide antioxidants: Novel neuroprotective agents. AAPS J. 2006;8:E521-E531
128. Szeto HH. Mitochondria-targeted cytoprotective peptides for ischemiareperfusion injury. Antioxid Redox Signal. 2008;10:601-619
129. Petri S, Kiaei M, Damiano M, et al. Cell-permeable peptide antioxidants as a novel therapeutic approach in a mouse model of amyotrophic lateral sclerosis. J Neurochem. 2006;98:1141-1148
130. Cho J, Won K, Wu D, et al. Potent mitochondria-targeted peptides reduce myocardial infarction in rats. Coron Artery Dis. 2007;18: 215-220
131. Dai DF, Chen T, Szeto H, et al. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol. 2011;58:73-82