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Pathophysiology of Cardiovascular Disease pp 23–33Cite as

Mitochondrial Function—A Limiting Factor in Heart Failure?

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 10))

Summary

Mitochondria are the major sources of energy for contraction in the heart, generating ATP from oxidative processes. The metabolic adaptations that occur in cardiac hypertrophy cause a switch in substrate provision from fatty acid to glucose oxidation. These modifications, together with depletion in critical cofactors and altered gene expression, may jeopardise mitochondrial function, resulting in apoptosis and cell loss. The progressive nature of these adaptations may underlie the transition from hypertrophy to heart failure.

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References

  1. Taegtmeyer H. 1994. Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol 19:62–113.

    Article  Google Scholar 

  2. Harmsen E, Seymour A-ML. 1988. The importance of the determination of ATP and catabolites. In “Myocardial Energy Metabolism” Eds de Jong JW. Publ: Martinus Nijhoff Dordrecht, Netherlands.

    Google Scholar 

  3. Balaban RS, Heinmann F. 1992. In “The Heart and the Cardiovascular System” Eds Fozzard H et al. Publ.

    Google Scholar 

  4. McCormack JG, Denton RM. 1989. Influence of calcium ions on mammalian intramitochondrial dehydrogenases. Meth Enzymol 174:95–118.

    Article  PubMed  CAS  Google Scholar 

  5. Chatham JC, Blackband SJ. 2001. NMR spectroscopy and imaging in animal research, IlAR Journal 42:189–208.

    Article  PubMed  CAS  Google Scholar 

  6. Rajagopalan B, Blackledge MJ, McKenna WJ, Bolas N, Radda GK. 1987. Measurement of phosphocreatine to ATP ratio in normal and diseased human heart by 31P magnetic resonance spectroscopy using the rotating frame-depth selection technique. Ann NY Acad Sci 508:321–332.

    Article  PubMed  CAS  Google Scholar 

  7. Raine AEG, Seymour A-ML, Roberts AFC, Radda GK, Ledingham JGG. 1993. Impairment of cardiac function and energetics in experimental renal failure. J Clin Invest 92:2934–2940.

    Article  PubMed  CAS  Google Scholar 

  8. Shulman RG, Rothman DL. 2001. 13C NMR of intermediary metabolism: Implications for Systemic Physiology. Annu Rev Physiol 63:15–48.

    Article  PubMed  Google Scholar 

  9. Chatham JC, Forder J, Glickson JD, Chance EM. 1995. Calculation of absolute flux and the elucidation of pathways of glutamate labelling in perfused rat hearts by 13C NMR spectroscopy. J Biol Chem 270:7999–8008.

    Article  PubMed  CAS  Google Scholar 

  10. Malloy CR, Sherry AD, Jeffrey FMH. 1990. Analysis of tricarboxylic acid cycle of the heart using 13C isotope isomers. Am J Physiol 259:H987–H995.

    PubMed  CAS  Google Scholar 

  11. Jeffrey FM, Dickzu V, Sherry AD, Malloy CR. 1995. Substrate selection in the isolated working rat heart. Basic Res Cardiol 90:38–396.

    Article  Google Scholar 

  12. Weiss RG, Chacko VP, Gerstenblith G. 1989. Fatty acid regulation of glucose metabolism in the intact beating rat heart assessed by carbon-13 NMR spectroscopy J Mol Cell Cardiol 21:469–478.

    Article  PubMed  CAS  Google Scholar 

  13. Clarke SJ. 2001. PhD Thesis, University of Hull.

    Google Scholar 

  14. Chatham JC, Seymour A-ML. 2002. Changes in cardiac metabolism precede development of contractile function in Type 2 diabetes. Cardiovas Res 55:104–112.

    Article  CAS  Google Scholar 

  15. Braunwald E, Bristow M. 2000. Congestive heart failure—fifty years of progress Circulation 102(suppl IV):14–23.

    Google Scholar 

  16. Boheler KR, Schwartz K. 1992. Gene expression in cardiac hypertrophy. Trends in Cardiovasc Med 2:172–178.

    Google Scholar 

  17. Depre C, Shipley Gl, Chen W, Han Q, Doenst T, Moore ML, Stepkowski S, Davies PJA, Taegtmeyer H. 1998. Unloaded heart in vivo replicates foetal gene expression of cardiac hypertrophy. Nature Med 4:1269–1275.

    Article  PubMed  CAS  Google Scholar 

  18. Rosenblatt-Velin N, Montessuit C, Papageoriou I, Terrand J, Lerch R. 2001. Postinfarction heart failure is associated with an upregulation of GLUT 1 and downregulation of genes of fatty acid metabolism. Cardiovasc Res 52:407–416.

    Article  PubMed  CAS  Google Scholar 

  19. Anveras P, Capasso JM. 1991. Loss of intermediary sized coronary arteries and capillary proliferation after left ventricular failure in rats. Am J Physiol 260:H1552–H2560.

    Google Scholar 

  20. Gaasch WH, Zie MR, Hoshino PK, Weinberg EO, Rhodes DR, Apstein CS. 1990. Tolerance of the hypertrophied heart to ischaemia. Circulation 81:1644–1653.

    Article  PubMed  CAS  Google Scholar 

  21. Schonekess BO, Allard MF, Lopaschuk GD 1996. Recovery of glycolysis and oxidative metabolism during postischemic reperfusion of hypertrophied hearts. Am J Physiol 271:H798–H805.

    PubMed  CAS  Google Scholar 

  22. Wambolt RB, Henning SL, English DR, Dyachkova Y, Lopaschuk GD, Allard M. 1999. Glucose utilisation and glycogen turnover are accelerated in hypertrophied hearts during severe low-flow ischemia. J Mol Cell Cardiol 31:493–502.

    Article  PubMed  CAS  Google Scholar 

  23. Ingwall JS. 1993. Is cardiac failure a consequence of decreased energy reserve? Circulation 87(sVII): 58–62.

    Google Scholar 

  24. Katz AM. 2001. Heart Failure in 2001—a prophecy revisited. Am J Cardiol 87:1383–1389.

    Article  PubMed  CAS  Google Scholar 

  25. Seymour A-ML, Eldar H, Radda GK. 1990. Hyperthyroidism results in increased glycolytic capacity in the rat heart—a 31-P NMR study. Biochim Biophys Acta 1055:107–116.

    Article  PubMed  CAS  Google Scholar 

  26. Smolenski RT, Jayakumar J, Seymour A-ML, Yacoub MH. 1998. Energy metabolism and mechanical recovery after cardioplegia in moderately hypertrophied rats. Molec Cell Biochem 180: 137–143.

    Article  PubMed  CAS  Google Scholar 

  27. Neubauer S, Horn M, Naumann A, Tian R, Hu K, Laser M, Friedrich J, Gaudron P, Schnackerz K, Ingwall JS, Ertl G. 1995. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction. J Clin Invest 95:1092–1100.

    Article  PubMed  CAS  Google Scholar 

  28. Tian R, Ingwall JS. 1996. Energetic basis for reduced contractile reserve in isolated hearts. Am J Physiol 270:H1207–H1216.

    PubMed  CAS  Google Scholar 

  29. Conway MA, Allis J, Ouwerkerk R, Niioka T, Rajagopalan B, Radda GK. 1991. Detection of low phosphocreatine/ATP ratio in failing hyprtrophied human myocardium by P-31 MRS. Lancet 338: 973–976.

    Article  PubMed  CAS  Google Scholar 

  30. Neubauer S, Krahe T, Schindler R, Horn M, Hillenbrand H, Enzeroth C, Mader H, Kromer E, Riegger G, Lackner K, Erd G. 1992. 31P MRS in dilated cardiomyopathy and coronary heart disease. Circulation 86:1810–1818.

    Article  PubMed  Google Scholar 

  31. Bottomley PA. 1989. Human in vivo NMR spectroscopy in diagnostic medicine: clinical tool or research probe? Radiol 170:1–15.

    CAS  Google Scholar 

  32. Swynghedauw B. 1999. Molecular mechanisms of myocardial remodelling. Physiol Rev 79:215–262.

    PubMed  CAS  Google Scholar 

  33. Lopaschuk GD, Belke DD, Gamble J, Ito T, Schonekess BO. 1994. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochim Biophys Acta 1213:263–276.

    Article  PubMed  CAS  Google Scholar 

  34. Russell RR, Taegtmeyer H. 1991. Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilising acetoacetate. J Clin Invest 87:384–390.

    Article  PubMed  CAS  Google Scholar 

  35. Russell RR, Taegtmeyer H. 1992. Coenzyme A sequestration in rat hearts oxidising ketone bodies. J Clin Invest 89:968–973.

    Article  PubMed  CAS  Google Scholar 

  36. Stanley WC. (ed) 2002. Special Issue on Myocardial energy metabolism in heart failure. Heart Failure Revs 7:113–219.

    Google Scholar 

  37. Paternostro G, Clarke K, Heath J, Seymour A-M, Radda GK. 1995. Decreased GLUT-4 mRNA content and insulin-sensitive deoxyglucose uptake show insulin resistance in the hypertensive rat heart. Cardiovasc Res 30:205–211.

    PubMed  CAS  Google Scholar 

  38. Zhang J, Duncker DJ, Ya X, Zhang Y, Pavek T, Wei H, Merkle H, Ugurbil K, From AHL, Bache RJ. 1995. Effect of left ventricular hypertrophy secondary to chronic pressure overload on transmural myocardial 2-deoxyglucose uptake—A 31P NMR spectroscopic study. Circulation 92:1274–1283.

    Article  PubMed  CAS  Google Scholar 

  39. Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD. 1994. Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol 267:H742–H750.

    PubMed  CAS  Google Scholar 

  40. Young ME, Laws FA, Goodwin G, Taegtmeyer H. 2001. Reactivation of PPARα is associated with contractile dysfunction in the hypertrophied rat heart. J Biol Chem 276:44390–44395.

    Article  PubMed  CAS  Google Scholar 

  41. Davila-Roman 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 40:271–277.

    Article  PubMed  CAS  Google Scholar 

  42. Collins-Nakai RL, Noseworthy D, Lopaschuk GD. 1994. Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. Am J Physiol 267:H1862–H1871.

    PubMed  CAS  Google Scholar 

  43. Dispersyn GD, Borgers M. 2001. Apoptosis in the heart: about programmed cell death and survival. News Physiol Sci 16:41–47.

    PubMed  CAS  Google Scholar 

  44. El Alaoui-Talibi Z, Landormy S, Loireau A, Moravec J. 1992. Fatty acid oxidation and mechanical performance of volume-overloaded rat hearts. Am J Physiol 262:H1068–H1074.

    PubMed  Google Scholar 

  45. Ben Cheikh R, Guendouz A, Moravec J. 1994. Control of oxidative metabolism in volume overloaded rat hearts: effects of different substrates. Am J Physiol 266:H2090–H2097.

    PubMed  Google Scholar 

  46. Reibel DK, Uboh CE, Kent RL. 1983. Altered coenzyme A and carnitine metabolism in pressure-overloaded hypertrophied hearts. Am J Physiol 244:H839–H843.

    PubMed  CAS  Google Scholar 

  47. El Alaoui-Talibi Z, Guendouz A, Moravec M, Moravec J. 1997. Control of oxidative metabolism in volume-overloaded rat hearts. Am J Physiol 272:H1615–H1624.

    PubMed  Google Scholar 

  48. Timmons JA, Poucher SM, Constantin-Teodosiu D, Worrall V, MacDonald I, Greenhaff PL. 1996. Increased acetyl groups availability enhances contractile function of canine skeltal muscle during ischemia. J Clin Invest 97:879–883.

    Article  PubMed  CAS  Google Scholar 

  49. Seymour A-ML, Chatham JC. 1997. The effects of hypertrophy and diabetes on cardiac pyruvate dehydrogenase activity. J Mol Cell Cardiol 29:2771–2778.

    Article  PubMed  CAS  Google Scholar 

  50. 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 33:1065–1089.

    Article  PubMed  CAS  Google Scholar 

  51. Halestrap A. 2000. Mitochondria and cell death. Biochemist 22(2): 19–24.

    CAS  Google Scholar 

  52. Anversa P, Leri A, Kajstura J, Nadal-Ginard B. 2002. Myocyte growth and cardiac repair. J Mol Cell Cardiol 34:91–105.

    Article  PubMed  CAS  Google Scholar 

  53. Green DR, Reed JC. 1998. Mitochondria and apoptosis. Science 281:1309–1316.

    Article  PubMed  CAS  Google Scholar 

  54. Kantor PF, Lucien A, Kozak R, Lopaschuk GD. 2000. Anti-anginal drug, trimetazidine, shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation. Circ Res 86:580–588.

    Article  PubMed  CAS  Google Scholar 

  55. Stanley WC, Hoppel CL. 2000. Mitochondrial dysfunction in heart failure: potential for therapeutic interventions? Cardiovasc Res 45:805–806.

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Biological Sciences, University of Hull, HU6 7RX, Cottingham Road, Hull, UK

    Dr Anne-Marie L. Seymour

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  1. Dr Anne-Marie L. Seymour
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Editor information

Editors and Affiliations

  1. Institute of Cardiovascular Sciences St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director) (Distinguished Professor and Director)

  2. Philipps University of Marburg, Marburg, Germany

    Heinz Rupp PhD (Professor of Medicine) (Professor of Medicine)

  3. Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Aubie Angel MD (Professor of Internal Medicine) (Professor of Internal Medicine)

  4. Division of Stroke & Vascular Disease St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Grant N. Pierce PhD, FACC (Professor & Director) (Professor & Director)

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© 2004 Springer Science+Business Media Dordrecht

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Seymour, AM.L. (2004). Mitochondrial Function—A Limiting Factor in Heart Failure?. In: Dhalla, N.S., Rupp, H., Angel, A., Pierce, G.N. (eds) Pathophysiology of Cardiovascular Disease. Progress in Experimental Cardiology, vol 10. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0453-5_2

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  • DOI: https://doi.org/10.1007/978-1-4615-0453-5_2

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5084-2

  • Online ISBN: 978-1-4615-0453-5

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