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.
Similar content being viewed by others
References
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
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
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
Katz AM (2009) Heart failure. Pathophysiology, molecular biology, and clinical management, 2nd edn. Lippincott Williams & Wilkins, Philadelphia
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
Katz AM (2006) Physiology of the heart, 4th edn. Lippincott Williams & Wilkins, Philadelphia
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
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
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
Abel ED, Doenst T (2011) Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res. doi:10.1093/cvr/cvr015
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
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
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
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
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
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
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
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
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
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
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
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
Gustafsson AB, Gottlieb RA (2003) Mechanisms of apoptosis in the heart. J Clin Immunol 23(6):447–459
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
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
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
Stanley WC, Chandler MP (2002) Energy metabolism in the normal and failing heart: potential for therapeutic interventions. Heart Fail Rev 7(2):115–130
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
Ashrafian H, Frenneaux MP, Opie LH (2007) Metabolic mechanisms in heart failure. Circulation 116(4):434–448. doi:10.1161/CIRCULATIONAHA.107.702795
Neubauer S (2007) The failing heart—an engine out of fuel. N Engl J Med 356(11):1140–1151. doi:10.1056/NEJMra063052
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
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
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
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
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
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
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
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
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
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
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
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
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
Taegtmeyer H (2002) Switching metabolic genes to build a better heart. Circulation 106(16):2043–2045. doi:10.1161/01.CIR.0000036760.42319.3F
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
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
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
Kornberg HL (1966) Anaplerotic sequences and their role in metabolism. Essays Biochem 2:1–31
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
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
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
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
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
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
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
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
Sambandam N, Lopaschuk GD, Brownsey RW, Allard MF (2002) Energy metabolism in the hypertrophied heart. Heart Fail Rev 7(2):161–173
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
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
Friehs I, del Nido PJ (2003) Increased susceptibility of hypertrophied hearts to ischemic injury. Ann Thorac Surg 75(2):S678–S684
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
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
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
Suga H (1990) Ventricular energetics. Physiol Rev 70(2):247–277
Semenza GL (2007) Oxygen-dependent regulation of mitochondrial respiration by hypoxia-inducible factor 1. Biochem J 405(1):1–9. doi:10.1042/BJ20070389
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
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
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
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
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
Saraste M (1999) Oxidative phosphorylation at the fin de siècle. Science 283(5407):1488–1493
Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic coupling. Glynn Research Ltd, Bodmin
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
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
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
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
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
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
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
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
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
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
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
Scarpulla RC (2008) Transcriptional paradigms in mammalian mitochondrial biogenesis and function. Physiol Rev 88(2):611–638. doi:10.1152/physrev.00025.2007
Casademont J, Miró O (2002) Electron transport chain defects in heart failure. Heart Fail Rev 7(2):131–139
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
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
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
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
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
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
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
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
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
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
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
Dröge W (2002) Free radicals in the physiological control of cell function. Physiol Rev 82(1):47–95. doi:10.1152/physrev.00018.2001
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
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
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
Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495. doi:10.1016/j.cell.2005.02.001
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
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
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
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
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
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
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
Giordano FJ (2005) Oxygen, oxidative stress, hypoxia, and heart failure. J Clin Invest 115(3):500–508. doi:10.1172/JCI24408
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10741-012-9346-7