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Alterations in mitochondrial function in cardiac hypertrophy and heart failure

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Abstract

Normal cardiac function requires high and continuous supply with ATP. As mitochondria are the major source of ATP production, it is apparent that mitochondrial function and cardiac function need to be closely related to each other. When subjected to overload, the heart hypertrophies. Initially, the development of hypertrophy is a compensatory mechanism, and contractile function is maintained. However, when the heart is excessively and/or persistently stressed, cardiac function may deteriorate, leading to the onset of heart failure. There is considerable evidence that alterations in mitochondrial function are involved in the decompensation of cardiac hypertrophy. Here, we review metabolic changes occurring at the mitochondrial level during the development of cardiac hypertrophy and the transition to heart failure. We will focus on changes in mitochondrial substrate metabolism, the electron transport chain and the role of oxidative stress. We will demonstrate that, with respect to mitochondrial adaptations, a clear distinction between hypertrophy and heart failure cannot be made because most of the findings present in overt heart failure can already be found in the various stages of hypertrophy.

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References

  1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM et al (2011) Heart disease and stroke statistics—2011 update: a report from the American Heart Association. Circulation 123(4):e18–e209. doi:10.1161/CIR.0b013e3182009701

    Article  PubMed  Google Scholar 

  2. Gheorghiade M, Pang PS (2009) Acute heart failure syndromes. J Am Coll Cardiol 53(7):557–573. doi:10.1016/j.jacc.2008.10.041

    Article  PubMed  Google Scholar 

  3. Bui AL, Horwich TB, Fonarow GC (2010) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8(1):30–41. doi:10.1038/nrcardio.2010.165

    Article  PubMed  Google Scholar 

  4. Katz AM (2009) Heart failure. Pathophysiology, molecular biology, and clinical management, 2nd edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  5. Mann DL (2012) Pathophysiology of heart failure. In: Bonow RO, Mann DL, Zipes DP, Libby P (eds) Braunwald’s heart disease. A textbook of cardiovascular medicine, vol 1, 9th edn. Elsevier Saunders, Philadelphia, pp 487–504

    Chapter  Google Scholar 

  6. Katz AM (2006) Physiology of the heart, 4th edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  7. Grossman W, Jones D, McLaurin LP (1975) Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 56(1):56–64. doi:10.1172/JCI108079

    Article  PubMed  CAS  Google Scholar 

  8. Gradman AH, Alfayoumi F (2006) From left ventricular hypertrophy to congestive heart failure: management of hypertensive heart disease. Prog Cardiovasc Dis 48(5):326–341. doi:10.1016/j.pcad.2006.02.001

    Article  PubMed  Google Scholar 

  9. De Boer RA, Pinto YM, Van Veldhuisen DJ (2003) The imbalance between oxygen demand and supply as a potential mechanism in the pathophysiology of heart failure: the role of microvascular growth and abnormalities. Microcirculation 10(2):113–126. doi:10.1038/sj.mn.7800188

    PubMed  Google Scholar 

  10. Abel ED, Doenst T (2011) Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res. doi:10.1093/cvr/cvr015

    Google Scholar 

  11. O’Neill BT, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, Guo A, Zaha VG, Davis DK, Schell JC (2007) A conserved role for phosphatidylinositol 3-kinase but not akt signaling in mitochondrial adaptations that accompany physiological cardiac hypertrophy. Cell Metab 6(4):294–306. doi:10.1016/j.cmet.2007.09.001

    Article  PubMed  CAS  Google Scholar 

  12. Wilkins BJ, Dai Y-S, Bueno OF, Parsons SA, Xu J, Plank DM, Jones F, Kimball TR, Molkentin JD (2004) Calcineurin/NFAT coupling participates in pathological, but not physiological, cardiac hypertrophy. Circ Res 94(1):110–118. doi:10.1161/01.RES.0000109415.17511.18

    Article  PubMed  CAS  Google Scholar 

  13. McMullen J, Jennings GL (2007) Differences between pathological and physiological cardiac hypertrophy: novel therapeutic strategies to treat heart failure. Clin Exp Pharmacol Physiol 34(4):255–262. doi:10.1111/j.1440-1681.2007.04585.x

    Article  PubMed  CAS  Google Scholar 

  14. Burelle Y (2004) Regular exercise is associated with a protective metabolic phenotype in the rat heart. Am J Physiol Heart Circ Physiol 287(3):H1055–H1063. doi:10.1152/ajpheart.00925.2003

    Article  PubMed  CAS  Google Scholar 

  15. Schoepe M, Schrepper A, Schwarzer M, Osterholt M, Doenst T (2012) Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity. Metabolism 61(1):117–126. doi:10.1016/j.metabol.2011.05.023

    Article  PubMed  CAS  Google Scholar 

  16. Chatterjee K, Massie B (2007) Systolic and diastolic heart failure: differences and similarities. J Card Fail 13(7):569–576. doi:10.1016/j.cardfail.2007.04.006

    Article  PubMed  Google Scholar 

  17. De Keulenaer GW, Brutsaert DL (2007) Systolic and diastolic heart failure: different phenotypes of the same disease? Eur J Heart Fail 9(2):136–143. doi:10.1016/j.ejheart.2006.05.014

    Article  PubMed  Google Scholar 

  18. Zile MR (2002) New concepts in diastolic dysfunction and diastolic heart failure: part II: causal mechanisms and treatment. Circulation 105(12):1503–1508. doi:10.1161/hc1202.105290

    Article  PubMed  Google Scholar 

  19. Lorell BH, Carabello BA (2000) Left ventricular hypertrophy : pathogenesis, detection, and prognosis. Circulation 102(4):470–479. doi:10.1161/01.CIR.102.4.470

    Article  PubMed  CAS  Google Scholar 

  20. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL (2001) Mitochondrial dysfunction in cardiac disease: ischemia–reperfusion, aging, and heart failure. J Mol Cell Cardiol 33(6):1065–1089. doi:10.1006/jmcc.2001.1378

    Article  PubMed  CAS  Google Scholar 

  21. Marin-Garcia J, Goldenthal MJ (2008) Mitochondrial centrality in heart failure. Heart Fail Rev 13(2):137–150. doi:10.1007/s10741-007-9079-1

    Article  PubMed  Google Scholar 

  22. Tsutsui H, Ide T, Kinugawa S (2006) Mitochondrial oxidative stress, DNA damage, and heart failure. Antioxid Redox Signal 8(9–10):1737–1744. doi:10.1089/ars.2006.8.1737

    Article  PubMed  CAS  Google Scholar 

  23. Gustafsson AB, Gottlieb RA (2003) Mechanisms of apoptosis in the heart. J Clin Immunol 23(6):447–459

    Article  PubMed  CAS  Google Scholar 

  24. Liu T, O’Rourke B (2009) Regulation of mitochondrial Ca2+ and its effects on energetics and redox balance in normal and failing heart. J Bioenerg Biomembr 41(2):127–132. doi:10.1007/s10863-009-9216-8

    Article  PubMed  CAS  Google Scholar 

  25. Ventura-Clapier R, Garnier A, Veksler V (2004) Energy metabolism in heart failure. J Physiol 555(Pt 1):1–13. doi:10.1113/jphysiol.2003.055095

    Article  PubMed  CAS  Google Scholar 

  26. Ferrari R, Cargnoni A, Ceconi C (2006) Anti-ischaemic effect of ivabradine. Pharmacol Res 53(5):435–439. doi:10.1016/j.phrs.2006.03.018

    Article  PubMed  CAS  Google Scholar 

  27. Stanley WC, Chandler MP (2002) Energy metabolism in the normal and failing heart: potential for therapeutic interventions. Heart Fail Rev 7(2):115–130

    Article  PubMed  CAS  Google Scholar 

  28. Taegtmeyer H, Golfman L, Sharma S, Razeghi P, van Arsdall M (2004) Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann N Y Acad Sci 1015:202–213. doi:10.1196/annals.1302.017

    Article  PubMed  CAS  Google Scholar 

  29. Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116(4):434–448. doi:10.1161/CIRCULATIONAHA.107.702795

    Article  PubMed  CAS  Google Scholar 

  30. Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356(11):1140–1151. doi:10.1056/NEJMra063052

    Article  PubMed  Google Scholar 

  31. Ingwall JS, Weiss RG (2004) Is the failing heart energy starved? On using chemical energy to support cardiac function. Circ Res 95(2):135–145. doi:10.1161/01.RES.0000137170.41939.d9

    Article  PubMed  CAS  Google Scholar 

  32. Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, Kochsiek K (1997) Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 96(7):2190–2196. doi:10.1161/01.cir.96.7.2190

    Article  PubMed  CAS  Google Scholar 

  33. Doenst T, Pytel G, Schrepper A, Amorim PA, Faerber G, Shingu Y, Mohr FW, Schwarzer M (2010) Decreased rates of substrate oxidation ex vivo predict the onset of heart failure and contractile dysfunction in rats with pressure overload. Cardiovasc Res. doi:10.1093/cvr/cvp414

    Google Scholar 

  34. Akki A, Smith K, Seymour A-ML (2008) Compensated cardiac hypertrophy is characterised by a decline in palmitate oxidation. Mol Cell Biol 311(1–2):215–224. doi:10.1007/s11010-008-9711-y

    CAS  Google Scholar 

  35. Sorokina N, O’Donnell JM, McKinney RD, Pound KM, Woldegiorgis G, LaNoue KF, Ballal K, Taegtmeyer H, Buttrick PM, Lewandowski ED (2007) Recruitment of compensatory pathways to sustain oxidative flux with reduced carnitine palmitoyltransferase I activity characterizes inefficiency in energy metabolism in hypertrophied hearts. Circulation 115(15):2033–2041. doi:10.1161/CIRCULATIONAHA.106.668665

    Article  PubMed  CAS  Google Scholar 

  36. Lydell CP, Chan A, Wambolt RB, Sambandam N, Parsons H, Bondy GP, Rodrigues B, Popov KM, Harris RA, Brownsey RW, Allard MF (2002) Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts. Cardiovasc Res 53(4):841–851

    Article  PubMed  CAS  Google Scholar 

  37. Allard MF, Wambolt RB, Longnus SL, Grist M, Lydell CP, Parsons HL, Rodrigues B, Hall JL, Stanley WC, Bondy GP (2000) Hypertrophied rat hearts are less responsive to the metabolic and functional effects of insulin. Am J Physiol Heart Circ Physiol 279(3):E487–E493

    CAS  Google Scholar 

  38. Fujii N (2004) Saturated glucose uptake capacity and impaired fatty acid oxidation in hypertensive hearts before development of heart failure. Am J Physiol Heart Circ Physiol 287(2):H760–H766. doi:10.1152/ajpheart.00734.2003

    Article  PubMed  CAS  Google Scholar 

  39. Degens H, de Brouwer KFJ, Gilde AJ, Lindhout M, Willemsen PHM, Janssen BJ, Vusse GJ, Van Bilsen M (2005) Cardiac fatty acid metabolism is preserved in the compensated hypertrophic rat heart. Basic Res Cardiol 101(1):17–26. doi:10.1007/s00395-005-0549-0

    Article  PubMed  CAS  Google Scholar 

  40. Remondino A (2000) Altered expression of proteins of metabolic regulation during remodeling of the left ventricle after myocardial infarction. J Mol Cell Cardiol 32(11):2025–2034. doi:10.1006/jmcc.2000.1234

    Article  PubMed  CAS  Google Scholar 

  41. Heather LC, Cole MA, Lygate CA, Evans RD, Stuckey D, Murray AJ, Neubauer S, Clarke K (2006) Fatty acid transporter levels and palmitate oxidation rate correlate with ejection fraction in the infarcted rat heart. Cardiovasc Res 72(3):430–437. doi:10.1016/j.cardiores.2006.08.020

    Article  PubMed  CAS  Google Scholar 

  42. Chandler MP, Kerner J, Huang H, Vazquez EJ, Reszko A, Martini WZ, Hoppel CL, Imai M, Rastogi S, Sabbah HN, Stanley WC (2004) Moderate severity heart failure does not involve a downregulation of myocardial fatty acid oxidation. Am J Physiol Heart Circ Physiol 287(4):H1538–H1543. doi:10.1152/ajpheart.00281.2004

    Article  PubMed  CAS  Google Scholar 

  43. O’Donnell JM, Fields AD, Sorokina N, Lewandowski ED (2008) The absence of endogenous lipid oxidation in early stage heart failure exposes limits in lipid storage and turnover. J Mol Cell Cardiol 44(2):315–322. doi:10.1016/j.yjmcc.2007.11.006

    Article  PubMed  CAS  Google Scholar 

  44. Taegtmeyer H (2002) Switching metabolic genes to build a better heart. Circulation 106(16):2043–2045. doi:10.1161/01.CIR.0000036760.42319.3F

    Article  PubMed  Google Scholar 

  45. Christe ME, Rodgers RL (1994) Altered glucose and fatty acid oxidation in hearts of the spontaneously hypertensive rat. J Mol Cell Cardiol 26(10):1371–1375. doi:10.1006/jmcc.1994.1155

    Article  PubMed  CAS  Google Scholar 

  46. Qanud K, Mamdani M, Pepe M, Khairallah RJ, Gravel J, Lei B, Gupte SA, Sharov VG, Sabbah HN, Stanley WC, Recchia FA (2008) Reverse changes in cardiac substrate oxidation in dogs recovering from heart failure. Am J Physiol Heart Circ Physiol 295(5):H2098–H2105. doi:10.1152/ajpheart.00471.2008

    Article  PubMed  CAS  Google Scholar 

  47. Leong HS, Brownsey RW, Kulpa JE, Allard MF (2003) Glycolysis and pyruvate oxidation in cardiac hypertrophy—why so unbalanced? Comp Biochem Physiol A: Mol Integr Physiol 135(4):499–513. doi:10.1016/S1095-6433(03)00007-2

    Article  CAS  Google Scholar 

  48. Kornberg HL (1966) Anaplerotic sequences and their role in metabolism. Essays Biochem 2:1–31

    CAS  Google Scholar 

  49. Lei B, Lionetti V, Young ME, Chandler MP, d’Agostino C, Kang E, Altarejos M, Matsuo K, Hintze TH, Stanley WC, Recchia FA (2004) Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. J Mol Cell Cardiol 36(4):567–576. doi:10.1016/j.yjmcc.2004.02.004

    Google Scholar 

  50. de Brouwer KFJ, Degens H, Aartsen WM, Lindhout M, Bitsch NJJE, Gilde AJ, Willemsen PHM, Janssen BJA, van der Vusse GJ, Van Bilsen M (2006) Specific and sustained down-regulation of genes involved in fatty acid metabolism is not a hallmark of progression to cardiac failure in mice. J Mol Cell Cardiol 40(6):838–845. doi:10.1016/j.yjmcc.2006.03.429

    Article  PubMed  CAS  Google Scholar 

  51. Randle PJ, Garland PB, Hales CN, Newsholme EA (1963) The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1(7285):785–789

    Article  PubMed  CAS  Google Scholar 

  52. Taegtmeyer H, Wilson CR, Razeghi P, Sharma S (2005) Metabolic energetics and genetics in the heart. Ann N Y Acad Sci 1047:208–218. doi:10.1196/annals.1341.019

    Article  PubMed  CAS  Google Scholar 

  53. Hue L, Taegtmeyer H (2009) The Randle cycle revisited: a new head for an old hat. Am J Physiol Endocrinol Metab 297(3):E578–E591. doi:10.1152/ajpendo.00093.2009

    Article  PubMed  CAS  Google Scholar 

  54. Finck BN, Kelly DP (2007) Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) regulatory cascade in cardiac physiology and disease. Circulation 115(19):2540–2548. doi:10.1161/CIRCULATIONAHA.107.670588

    Article  PubMed  Google Scholar 

  55. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP (1996) Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 94(11):2837–2842

    Article  PubMed  CAS  Google Scholar 

  56. Osorio JC (2002) Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure. Circulation 106(5):606–612. doi:10.1161/01.CIR.0000023531.22727.C1

    Article  PubMed  CAS  Google Scholar 

  57. Sambandam N, Lopaschuk GD, Brownsey RW, Allard MF (2002) Energy metabolism in the hypertrophied heart. Heart Fail Rev 7(2):161–173

    Article  PubMed  CAS  Google Scholar 

  58. van der Vusse GJ, Van Bilsen M, Glatz JF (2000) Cardiac fatty acid uptake and transport in health and disease. Cardiovasc Res 45(2):279–293

    Article  PubMed  Google Scholar 

  59. Schwenk RW, Luiken JJFP, Bonen A, Glatz JFC (2008) Regulation of sarcolemmal glucose and fatty acid transporters in cardiac disease. Cardiovasc Res 79(2):249–258. doi:10.1093/cvr/cvn116

    Article  PubMed  CAS  Google Scholar 

  60. Friehs I, del Nido PJ (2003) Increased susceptibility of hypertrophied hearts to ischemic injury. Ann Thorac Surg 75(2):S678–S684

    Article  PubMed  Google Scholar 

  61. Anversa P, Ricci R, Olivetti G (1986) Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: a review. J Am Coll Cardiol 7(5):1140–1149. doi:10.1016/S0735-1097(86)80236-4

    Article  PubMed  CAS  Google Scholar 

  62. Sabbah HN, Sharov VG, Lesch M, Goldstein S (1995) Progression of heart failure: a role for interstitial fibrosis. Mol Cell Biochem 147(1–2):29–34

    Article  PubMed  CAS  Google Scholar 

  63. Stanley WC, Recchia FA, Lopaschuk GD (2005) Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 85(3):1093–1129. doi:10.1152/physrev.00006.2004

    Article  PubMed  CAS  Google Scholar 

  64. Suga H (1990) Ventricular energetics. Physiol Rev 70(2):247–277

    PubMed  CAS  Google Scholar 

  65. Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405(1):1–9. doi:10.1042/BJ20070389

    PubMed  CAS  Google Scholar 

  66. Webster KA, Gunning P, Hardeman E, Wallace DC, Kedes L (1990) Coordinate reciprocal trends in glycolytic and mitochondrial transcript accumulations during the in vitro differentiation of human myoblasts. J Cell Physiol 142(3):566–573. doi:10.1002/jcp.1041420316

    Article  PubMed  CAS  Google Scholar 

  67. de las Fuentes L, Soto P, Cupps B, Pasque M, Herrero P, Gropler R, Waggoner A, Dávila-Román VG (2006) Hypertensive left ventricular hypertrophy is associated with abnormal myocardial fatty acid metabolism and myocardial efficiency. J Nucl Cardiol 13(3):369–377. doi:10.1016/j.nuclcard.2006.01.021

    Article  PubMed  Google Scholar 

  68. Dávila-Román VG, Vedala G, Herrero P, de las Fuentes L, Rogers JG, Kelly DP, Gropler RJ (2002) Altered myocardial fatty acid and glucose metabolism in idiopathic dilated cardiomyopathy. J Am Coll Cardiol 40(2):271–277

    Article  PubMed  Google Scholar 

  69. Tuunanen H, Engblom E, Naum A, Scheinin M, Någren K, Airaksinen J, Nuutila P, Iozzo P, Ukkonen H, Knuuti J (2006) Decreased myocardial free fatty acid uptake in patients with idiopathic dilated cardiomyopathy: evidence of relationship with insulin resistance and left ventricular dysfunction. J Card Fail 12(8):644–652. doi:10.1016/j.cardfail.2006.06.005

    Article  PubMed  CAS  Google Scholar 

  70. Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069. doi:10.1146/annurev.bi.54.070185.005055

    Article  PubMed  CAS  Google Scholar 

  71. Saraste M (1999) Oxidative phosphorylation at the fin de siècle. Science 283(5407):1488–1493

    Article  PubMed  CAS  Google Scholar 

  72. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic coupling. Glynn Research Ltd, Bodmin

    Google Scholar 

  73. Osterholt M, Schwarzer M, Schrepper A, Amorim PA, Mohr FW, Doenst T (2010) Diminished complex I activity as possible contributor to reduced respiratory capacity in pressure overload heart failure. Clin Res Cardiol 99(Suppl 1):P1302

    Google Scholar 

  74. Heather LC, Carr C, Stuckey D, Pope S, Morten K, Carter E, Edwards LM, Clarke K (2010) Critical role of complex III in the early metabolic changes following myocardial infarction. Cardiovasc Res 85(1):127–136. doi:10.1093/cvr/cvp276

    Article  PubMed  CAS  Google Scholar 

  75. Rennison JH, McElfresh TA, Okere IC, Vazquez EJ, Patel HV, Foster AB, Patel KK, Chen Q, Hoit BD, Tserng K-Y, Hassan MO, Hoppel CL, Chandler MP (2007) High-fat diet postinfarction enhances mitochondrial function and does not exacerbate left ventricular dysfunction. Am J Physiol Heart Circ Physiol 292(3):H1498–H1506. doi:10.1152/ajpheart.01021.2006

    Article  PubMed  CAS  Google Scholar 

  76. Marin-Garcia J, Goldenthal MJ, Moe GW (2001) Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure. Cardiovasc Res 52(1):103–110

    Article  PubMed  CAS  Google Scholar 

  77. Marin-Garcia J, Goldenthal MJ, Damle S, Pi Y, Moe GW (2009) Regional distribution of mitochondrial dysfunction and apoptotic remodeling in pacing-induced heart failure. J Card Fail 15(8):700–708. doi:10.1016/j.cardfail.2009.04.010

    Article  PubMed  CAS  Google Scholar 

  78. Ide T, Tsutsui H, Kinugawa S, Utsumi H, Kang D, Hattori N, Uchida K, Arimura K, Egashira K, Takeshita A (1999) Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myocardium. Circ Res 85(4):357–363

    Article  PubMed  CAS  Google Scholar 

  79. Sparagna GC, Chicco AJ, Murphy RC, Bristow MR, Johnson CA, Rees ML, Maxey ML, McCune SA, Moore RL (2007) Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure. J Lipid Res 48(7):1559–1570. doi:10.1194/jlr.M600551-JLR200

    Article  PubMed  CAS  Google Scholar 

  80. Scheubel RJ, Tostlebe M, Simm A, Rohrbach S, Prondzinsky R, Gellerich FN, Silber RE, Holtz J (2002) 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):2174–2181

    Article  PubMed  CAS  Google Scholar 

  81. Lemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43(12):1729–1738. doi:10.1016/j.biocel.2011.08.008

    Article  PubMed  CAS  Google Scholar 

  82. Buchwald A, Till H, Unterberg C, Oberschmidt R, Figulla HR, Wiegand V (1990) Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy. Eur Heart J 11(6):509–516

    PubMed  CAS  Google Scholar 

  83. Jarreta D, Orús J, Barrientos A, Miró O, Roig E, Heras M, Moraes CT, Cardellach F, Casademont J (2000) Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy. Cardiovasc Res 45(4):860–865

    Article  PubMed  CAS  Google Scholar 

  84. Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88(2):611–638. doi:10.1152/physrev.00025.2007

    Article  PubMed  CAS  Google Scholar 

  85. Casademont J, Miró O (2002) Electron transport chain defects in heart failure. Heart Fail Rev 7(2):131–139

    Article  PubMed  CAS  Google Scholar 

  86. Kim UK, Kim HS, Oh BH, Lee MM, Kim SH, Chae JJ, Choi HS, Choe SC, Lee CC, Park YB (2000) Analysis of mitochondrial DNA deletions in four chambers of failing human heart: hemodynamic stress, age, and disease are important factors. Basic Res Cardiol 95(2):163–171

    Article  PubMed  CAS  Google Scholar 

  87. Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A (2001) Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res 88(5):529–535. doi:10.1161/01.RES.88.5.529

    Article  PubMed  CAS  Google Scholar 

  88. Hansson A, Hance N, Dufour E, Rantanen A, Hultenby K, Clayton DA, Wibom R, Larsson N-G (2004) A switch in metabolism precedes increased mitochondrial biogenesis in respiratory chain-deficient mouse hearts. Proc Natl Acad Sci USA 101(9):3136–3141. doi:10.1073/pnas.0308710100

    Article  PubMed  CAS  Google Scholar 

  89. Karamanlidis G, Nascimben L, Couper GS, Shekar PS, del Monte F, Tian R (2010) Defective DNA replication impairs mitochondrial biogenesis in human failing hearts. Circ Res 106(9):1541–1548. doi:10.1161/CIRCRESAHA.109.212753

    Article  PubMed  CAS  Google Scholar 

  90. Bugger H, Schwarzer M, Chen D, Schrepper A, Amorim PA, Schoepe M, Nguyen TD, Mohr FW, Khalimonchuk O, Weimer BC, Doenst T (2010) Proteomic remodelling of mitochondrial oxidative pathways in pressure overload-induced heart failure. Cardiovasc Res 85(2):376–384. doi:10.1093/cvr/cvp344

    Article  PubMed  CAS  Google Scholar 

  91. Heinke MY, Wheeler CH, Yan JX, Amin V, Chang D, Einstein R, Dunn MJ, dos Remedios CG (1999) Changes in myocardial protein expression in pacing-induced canine heart failure. Electrophoresis 20(10):2086–2093

    Article  PubMed  CAS  Google Scholar 

  92. Jüllig M, Hickey AJR, Chai CC, Skea GL, Middleditch MJ, Costa S, Choong SY, Philips ARJ, Cooper GJS (2008) Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats. Proteomics 8(12):2556–2572. doi:10.1002/pmic.200700977

    Article  PubMed  CAS  Google Scholar 

  93. Hammer E, Goritzka M, Ameling S, Darm K, Steil L, Klingel K, Trimpert C, Herda LR, Dörr M, Kroemer HK, Kandolf R, Staudt A, Felix SB, Völker U (2011) Characterization of the human myocardial proteome in inflammatory dilated cardiomyopathy by label-free quantitative shotgun proteomics of heart biopsies. J Proteome Res 10(5):2161–2171. doi:10.1021/pr1008042

    Article  PubMed  CAS  Google Scholar 

  94. Tsutsui H, Kinugawa S, Matsushima S (2009) Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res 81(3):449–456. doi:10.1093/cvr/cvn280

    Article  PubMed  CAS  Google Scholar 

  95. Tsutsui H, Kinugawa S, Matsushima S (2011) Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301(6):H2181–H2190. doi:10.1152/ajpheart.00554.2011

    Article  PubMed  CAS  Google Scholar 

  96. Seddon M, Looi YH, Shah AM (2007) Oxidative stress and redox signalling in cardiac hypertrophy and heart failure. Heart 93(8):903–907. doi:10.1136/hrt.2005.068270

    Article  PubMed  CAS  Google Scholar 

  97. Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1):47–95. doi:10.1152/physrev.00018.2001

    PubMed  Google Scholar 

  98. Canton M, Menazza S, Sheeran FL, de Laureto PP, Di Lisa F, Pepe S (2011) Oxidation of myofibrillar proteins in human heart failure. J Am Coll Cardiol 57(3):300–309. doi:10.1016/j.jacc.2010.06.058

    Article  PubMed  CAS  Google Scholar 

  99. Barth E, Stämmler G, Speiser B, Schaper J (1992) Ultrastructural quantitation of mitochondria and myofilaments in cardiac muscle from 10 different animal species including man. J Mol Cell Cardiol 24(7):669–681

    Article  PubMed  CAS  Google Scholar 

  100. Sheeran FL, Pepe S (2006) Energy deficiency in the failing heart: linking increased reactive oxygen species and disruption of oxidative phosphorylation rate. Biochim Biophys Acta 1757(5–6):543–552. doi:10.1016/j.bbabio.2006.03.008

    PubMed  CAS  Google Scholar 

  101. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495. doi:10.1016/j.cell.2005.02.001

    Article  PubMed  CAS  Google Scholar 

  102. Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel J-L, Hasenfuss G, Shah AM (2003) Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41(12):2164–2171. doi:10.1016/S0735-1097(03)00471-6

    Article  PubMed  CAS  Google Scholar 

  103. Sam F, Kerstetter DL, Pimental DR, Mulukutla S, Tabaee A, Bristow MR, Colucci WS, Sawyer DB (2005) Increased reactive oxygen species production and functional alterations in antioxidant enzymes in human failing myocardium. J Card Fail 11(6):473–480. doi:10.1016/j.cardfail.2005.01.007

    Article  PubMed  CAS  Google Scholar 

  104. Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintrón M, Chen T, Marcinek DJ, Dorn GW, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS (2011) Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Gαq overexpression-induced heart failure. Circ Res 108(7):837–846. doi:10.1161/CIRCRESAHA.110.232306

    Article  PubMed  CAS  Google Scholar 

  105. Lunkenbein A, Amorim PA, Schrepper A, Schwarzer M, Mohr FW, Doenst T (2010) Pressure overload—induced hypertrophy is linked to an increase in mitochondrial ROS—production. Clin Res Cardiol 99(Suppl 1):V536

    Google Scholar 

  106. Schwarzer M, Osterholt M, Lunkenbein A, Schrepper A, Amorim PA, Doenst T (2011) Role of mitochondrial ROS-production in pressure overload induced heart failure in rats. Paper presented at the SHVM 2011, Brussels, Belgium

  107. Li JM (2002) Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40(4):477–484. doi:10.1161/01.HYP.0000032031.30374.32

    Article  PubMed  CAS  Google Scholar 

  108. Dhalla AK, Hill MF, Singal PK (1996) Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 28(2):506–514. doi:10.1016/0735-1097(96)00140-4

    Article  PubMed  CAS  Google Scholar 

  109. Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115(3):500–508. doi:10.1172/JCI24408

    PubMed  CAS  Google Scholar 

  110. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P (2000) Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 342(3):154–160. doi:10.1056/NEJM200001203420302

    Article  PubMed  CAS  Google Scholar 

  111. Keith ME, Jeejeebhoy KN, Langer A, Kurian R, Barr A, O’Kelly B, Sole MJ (2001) A controlled clinical trial of vitamin E supplementation in patients with congestive heart failure. Am J Clin Nutr 73(2):219–224

    PubMed  CAS  Google Scholar 

  112. Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J (2010) Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res 106(7):1253–1264. doi:10.1161/CIRCRESAHA.109.213116

    Article  PubMed  CAS  Google Scholar 

  113. Kuroda J, Ago T, Matsushima S, Zhai P, Schneider MD, Sadoshima J (2010) NADPH oxidase 4 (Nox4) is a major source of oxidative stress in the failing heart. Proc Natl Acad Sci USA 107(35):15565–15570. doi:10.1073/pnas.1002178107

    Article  PubMed  CAS  Google Scholar 

  114. O’Rourke B, Van Eyk JE, Foster DB (2011) Mitochondrial protein phosphorylation as a regulatory modality: implications for mitochondrial dysfunction in heart failure. Congest Heart Fail 17(6):269–282. doi:10.1111/j.1751-7133.2011.00266.x

    Article  PubMed  CAS  Google Scholar 

  115. Foster DB, Van Eyk JE, Marbán E, O’Rourke B (2009) Redox signaling and protein phosphorylation in mitochondria: progress and prospects. J Bioenerg Biomembr 41(2):159–168. doi:10.1007/s10863-009-9217-7

    Article  PubMed  CAS  Google Scholar 

  116. Schulman IH, Hare JM (2012) Regulation of cardiovascular cellular processes by S-nitrosylation. BBA Gen Subj 1820(6):752–762. doi:10.1016/j.bbagen.2011.04.002

    Article  CAS  Google Scholar 

  117. Sack MN (2011) Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart. Am J Physiol Heart Circ Physiol 301(6):H2191–H2197. doi:10.1152/ajpheart.00199.2011

    Article  PubMed  CAS  Google Scholar 

  118. Linn TC, Pettit FH, Reed LJ (1969) Alpha-keto acid dehydrogenase complexes. X. Regulation of the activity of the pyruvate dehydrogenase complex from beef kidney mitochondria by phosphorylation and dephosphorylation. Proc Natl Acad Sci USA 62(1):234–241

    Article  PubMed  CAS  Google Scholar 

  119. Papa S, De Rasmo D, Scacco S, Signorile A, Technikova-Dobrova Z, Palmisano G, Sardanelli AM, Papa F, Panelli D, Scaringi R, Santeramo A (2008) Mammalian complex I: A regulable and vulnerable pacemaker in mitochondrial respiratory function. Biochim Biophys Acta 1777(7–8):719–728

    PubMed  CAS  Google Scholar 

  120. Zhao X, Leon IR, Bak S, Mogensen M, Wrzesinski K, Hojlund K, Jensen ON (2010) Phosphoproteome analysis of functional mitochondria isolated from resting human muscle reveals extensive phosphorylation of inner membrane protein complexes and enzymes. Mol Cell Proteomics 10(1):M110.000299–M000110.000299. doi:10.1074/mcp.M110.000299

  121. Helling S, Vogt S, Rhiel A, Ramzan R, Wen L, Marcus K, Kadenbach B (2008) Phosphorylation and kinetics of mammalian cytochrome c oxidase. Mol Cell Proteomics 7(9):1714–1724. doi:10.1074/mcp.M800137-MCP200

    Article  PubMed  CAS  Google Scholar 

  122. Houtkooper RH, Pirinen E, Auwerx J (2012) Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol 13(4):225–238. doi:10.1038/nrm3293

    PubMed  CAS  Google Scholar 

  123. Sack MN (2011) The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging. J Mol Cell Cardiol:1–6. doi:10.1016/j.yjmcc.2011.11.004

  124. Tanno M, Kuno A, Horio Y, Miura T (2012) Emerging beneficial roles of sirtuins in heart failure. Basic Res Cardiol 107(4):273. doi:10.1007/s00395-012-0273-5

    Article  PubMed  CAS  Google Scholar 

  125. Sundaresan NR, Pillai VB, Gupta MP (2011) Emerging roles of SIRT1 deacetylase in regulating cardiomyocyte survival and hypertrophy. J Mol Cell Cardiol 51(4):614–618. doi:10.1016/j.yjmcc.2011.01.008

    Article  PubMed  CAS  Google Scholar 

  126. Kawashima T, Inuzuka Y, Okuda J, Kato T, Niizuma S, Tamaki Y, Iwanaga Y, Kawamoto A, Narazaki M, Matsuda T, Adachi S, Takemura G, Kita T, Kimura T, Shioi T (2011) Constitutive SIRT1 overexpression impairs mitochondria and reduces cardiac function in mice. J Mol Cell Cardiol 51(6):1026–1036. doi:10.1016/j.yjmcc.2011.09.013

    Article  PubMed  CAS  Google Scholar 

  127. Pillai VB, Sundaresan NR, Jeevanandam V, Gupta MP (2010) Mitochondrial SIRT3 and heart disease. Cardiovasc Res 88(2):250–256. doi:10.1093/cvr/cvq250

    Article  PubMed  CAS  Google Scholar 

  128. Cimen H, Han M-J, Yang Y, Tong Q, Koc H, Koc EC (2010) Regulation of succinate dehydrogenase activity by SIRT3 in mammalian mitochondria. Biochemistry 49(2):304–311. doi:10.1021/bi901627u

    Article  PubMed  CAS  Google Scholar 

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Osterholt, M., Nguyen, T.D., Schwarzer, M. et al. Alterations in mitochondrial function in cardiac hypertrophy and heart failure. Heart Fail Rev 18, 645–656 (2013). https://doi.org/10.1007/s10741-012-9346-7

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