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Cardiac Dysfunction and Metabolism: Unravelling the Molecular Cross-Talk

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Molecular Defects in Cardiovascular Disease

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Abstract

The interactions between cardiac metabolism and function at the molecular level are complex, but can be understood in terms of several broad concepts. First, function and metabolism are linked by acute mechanisms involving coupling of ATP demand to ATP synthesis, AMPK activation and various covalent and allosteric modifications of key enzymes, and by transcriptional mechanisms. Second, altered metabolic fluxes are not primary causes of cardiac injury; injury is caused by the cytoplasmic accumulation of toxic metabolic intermediates. These intermediates accumulate when there is a mismatch between the supply and utilization of metabolic fuels, and this can be produced either by excessive supply or reduced metabolic flux of a fuel. Third, changes in metabolism can be adaptive (as occurs in physiological hypertrophy), maladaptive in parallel with cardiac dysfunction (as occurs in pathological hypertrophy), or maladaptive as an antecedent and cause of cardiac dysfunction (as occurs in pathological hypertrophy). Finally, from an evolutionary perspective, disease results when the metabolic and functional phenotype is inappropriate for the environment; this can result from a phenotypically inappropriate response (e.g. pathological hypertrophy), or from a constraint that prevents the heart from adapting appropriately (e.g. reduced metabolic reserve). This book chapter reviews the latest evidence that is emerging about the operation of interactions between metabolism and function at the metabolic level in terms of these key concepts.

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References

  1. Allard MF, Schonekess BO, Henning SL, English DR, Lopaschuk GD. Contribution of oxidative metabolism and glycolysis to ATP production in hypertrophied hearts. Am J Physiol Heart Circ Physiol. 1994;267:H742–50.

    CAS  Google Scholar 

  2. Zhang J, Duncker DJ, Ya X, et al. Effect of left ventricular hypertrophy secondary to chronic pressure overload on transmural myocardial 2-deoxyglucose uptake. A 31P NMR spectroscopic study. Circulation. 1995;92:1274–83.

    PubMed  CAS  Google Scholar 

  3. Apstein CS. Glucose-insulin-potassium for acute myocardial infarction: remarkable results from a new prospective, randomized trial. Circulation. 1998;98:2223–6.

    PubMed  CAS  Google Scholar 

  4. Chatham JC, Forder JR, McNeill JH. The heart in diabetes. Norwell, MA: Kluwer; 1996.

    Google Scholar 

  5. Severson DL. Diabetic cardiomyopathy: recent evidence from mouse models of type 1 and type 2 diabetes. Can J Physiol Pharmacol. 2004;82:813–23.

    PubMed  CAS  Google Scholar 

  6. Brown GC. Control of respiration and ATP synthesis in mammalian mitochondria and cells. Biochem J. 1992;284:1–13.

    PubMed  CAS  Google Scholar 

  7. Saks VA, Kuznetsov AV, Vendelin M, et al. Functional coupling as a basic mechanism of feedback regulation of cardiac energy metabolism. Mol Cell Biochem. 2004;256–257:185–99.

    PubMed  Google Scholar 

  8. Carling D. The AMP-activated protein kinase cascade – a unifying system for energy control. Trends Biochem Sci. 2004;29:18–24.

    PubMed  CAS  Google Scholar 

  9. Keul J, Doll E, Keppler D, et al. Variations of arterial substrate level under the influence of physical work. Int Z Angew Physiol. 1966;22:356–85.

    PubMed  CAS  Google Scholar 

  10. Lopaschuk GD. Optimizing cardiac energy metabolism: how can fatty acid and carbohydrate metabolism be manipulated? Coron Artery Dis. 2001;12 Suppl 1:S8–11.

    PubMed  Google Scholar 

  11. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev. 2005;85:1093–129.

    PubMed  CAS  Google Scholar 

  12. Avogaro A, Nosadini R, Doria A, et al. Myocardial metabolism in insulin-deficient diabetic humans without coronary artery disease. Am J Physiol Endocrinol Metab. 1990;258:E606–18.

    CAS  Google Scholar 

  13. Hall JL, Stanley WC, Lopaschuk GD, et al. Impaired pyruvate oxidation but normal glucose uptake in diabetic pig heart during dobutamine-induced work. Am J Physiol Heart Circ Physiol. 1996;271:H2320–9.

    CAS  Google Scholar 

  14. Stanley WC, Lopaschuk GD, Hall JL, et al. Regulation of myocardial carbohydrate metabolism under normal and ischaemic conditions. Potential for pharmacological interventions. Cardiovasc Res. 1997;33:243–57.

    PubMed  CAS  Google Scholar 

  15. Young LH, Coven DL, Russell III RR. Cellular and molecular regulation of cardiac glucose transport. J Nucl Cardiol. 2000;7:267–76.

    PubMed  CAS  Google Scholar 

  16. Randle PJ. Fuel selection in animals. Biochem Soc Trans. 1986;14:799–806.

    PubMed  CAS  Google Scholar 

  17. Augustus AS, Kako Y, Yagyu H, et al. Routes of FA delivery to cardiac muscle: modulation of lipoprotein lipolysis alters uptake of TG-derived FA. Am J Physiol Endocrinol Metab. 2003;284:E331–9.

    PubMed  CAS  Google Scholar 

  18. Lopaschuk GD, Belke DD, Gamble J, et al. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochim Biophys Acta. 1994;1213:263–76.

    PubMed  CAS  Google Scholar 

  19. Bielawska AE, Shapiro JP, Jiang L, et al. Ceramide is involved in triggering of cardiomyocyte apoptosis induced by ischemia and reperfusion. Am J Pathol. 1997;151:1257–63.

    PubMed  CAS  Google Scholar 

  20. Bing RJ, Siegel A, Ungar I, et al. Metabolism of the human heart. II. Studies on fat, ketone and amino acid metabolism. Am J Med. 1954;16:504–15.

    PubMed  CAS  Google Scholar 

  21. Opie L. The heart: physiology, from cell to circulation. Philadelphia, PA: Lippincot-Raven; 1998.

    Google Scholar 

  22. Kerner J, Hoppel C. Fatty acid import into mitochondria. Biochim Biophys Acta. 2000;1486:1–17.

    PubMed  CAS  Google Scholar 

  23. McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem. 1997;244:1–14.

    PubMed  CAS  Google Scholar 

  24. McGarry JD, Mills SE, Long CS, et al. Observations on the affinity for carnitine, and malonyl-CoA sensitivity, of carnitine palmitoyltransferase I in animal and human tissues. Demonstration of the presence of malonyl-CoA in non-hepatic tissues of the rat. Biochem J. 1983;214:21–8.

    PubMed  CAS  Google Scholar 

  25. Scarpulla RC. Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta. 2002;1576:1–14.

    PubMed  CAS  Google Scholar 

  26. Francis GA, Annicotte JS, Auwerx J. PPAR-alpha effects on the heart and other vascular tissues. Am J Physiol Heart Circ Physiol. 2003;285:H1–9.

    PubMed  CAS  Google Scholar 

  27. Arany Z, He H, Lin J, et al. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005;1:259–71.

    PubMed  CAS  Google Scholar 

  28. Lehman JJ, Barger PM, Kovacs A, et al. Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest. 2000;106:847–56.

    PubMed  CAS  Google Scholar 

  29. Huss JM, Torra IP, Staels B, et al. Estrogen-related receptor alpha directs peroxisome proliferator-activated receptor alpha signaling in the transcriptional control of energy metabolism in cardiac and skeletal muscle. Mol Cell Biol. 2004;24:9079–91.

    PubMed  CAS  Google Scholar 

  30. Huss JM, Kelly DP. Nuclear receptor signaling and cardiac energetics. Circ Res. 2004;95:568–78.

    PubMed  CAS  Google Scholar 

  31. Rohini A, Agrawal N, Koyani CN, et al. Molecular targets and regulators of cardiac hypertrophy. Pharmacol Res. 2010;61:269–80.

    PubMed  CAS  Google Scholar 

  32. Dorn 2nd GW, Robbins J, Sugden PH. Phenotyping hypertrophy: eschew obfuscation. Circ Res. 2003;92:1171–5.

    PubMed  CAS  Google Scholar 

  33. Labarthe F, Khairallah M, Bouchard B, et al. Fatty acid oxidation and its impact on response of spontaneously hypertensive rat hearts to an adrenergic stress: benefits of a medium-chain fatty acid. Am J Physiol Heart Circ Physiol. 2005;288:H1425–36.

    PubMed  CAS  Google Scholar 

  34. Nascimben L, Ingwall JS, Lorell BH, et al. Mechanisms for increased glycolysis in the hypertrophied rat heart. Hypertension. 2004;44:662–7.

    PubMed  CAS  Google Scholar 

  35. Vincent G, Khairallah M, Bouchard B, et al. Metabolic phenotyping of the diseased rat heart using 13C-substrates and ex vivo perfusion in the working mode. Mol Cell Biochem. 2003;242:89–99.

    PubMed  CAS  Google Scholar 

  36. Bishop SP, Altschuld RA. Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Physiol. 1970;218:153–9.

    PubMed  CAS  Google Scholar 

  37. Overturf M, Sybers H, Schaper J, et al. Hypertension and atherosclerosis in cholesterol-fed rabbits. II. One-kidney, one clip Goldblatt hypertension treated with nifedipine. Atherosclerosis. 1987;66:63–76.

    PubMed  CAS  Google Scholar 

  38. Allard MF, Parsons HL, Saeedi R, et al. AMPK and metabolic adaptation by the heart to pressure overload. Am J Physiol Heart Circ Physiol. 2007;292:H140–8.

    PubMed  CAS  Google Scholar 

  39. Saeedi R, Saran VV, Wu SS, et al. AMP-activated protein kinase influences metabolic remodeling in H9c2 cells hypertrophied by arginine vasopressin. Am J Physiol Heart Circ Physiol. 2009;296:H1822–32.

    PubMed  CAS  Google Scholar 

  40. Sambandam N, Lopaschuk GD, Brownsey RW, et al. Energy metabolism in the hypertrophied heart. Heart Fail Rev. 2002;7:161–73.

    PubMed  CAS  Google Scholar 

  41. Barger PM, Brandt JM, Leone TC, et al. Deactivation of peroxisome proliferator-activated receptor-alpha during cardiac hypertrophic growth. J Clin Invest. 2000;105:1723–30.

    PubMed  CAS  Google Scholar 

  42. Jamshidi Y, Montgomery HE, Hense HW, et al. Peroxisome proliferator-activated receptor alpha gene regulates left ventricular growth in response to exercise and hypertension. Circulation. 2002;105:950–5.

    PubMed  CAS  Google Scholar 

  43. Sakai S, Miyauchi T, Irukayama-Tomobe Y, et al. Peroxisome proliferator-activated receptor-gamma activators inhibit endothelin-1-related cardiac hypertrophy in rats. Clin Sci (Lond). 2002;103 Suppl 48:16S–20.

    CAS  Google Scholar 

  44. Asakawa M, Takano H, Nagai T, et al. Peroxisome proliferator-activated receptor gamma plays a critical role in inhibition of cardiac hypertrophy in vitro and in vivo. Circulation. 2002;105:1240–6.

    PubMed  CAS  Google Scholar 

  45. Sivarajah A, McDonald MC, Thiemermann C. The cardioprotective effects of preconditioning with endotoxin, but not ischemia, are abolished by a peroxisome proliferator-activated receptor-gamma antagonist. J Pharmacol Exp Ther. 2005;313:896–901.

    PubMed  CAS  Google Scholar 

  46. Molkentin JD, Lu JR, Antos CL, et al. A calcineurin-dependent transcriptional pathway for cardiac hypertrophy. Cell. 1998;93:215–28.

    PubMed  CAS  Google Scholar 

  47. Bao Y, Li R, Jiang J, et al. Activation of peroxisome proliferator-activated receptor gamma inhibits endothelin-1-induced cardiac hypertrophy via the calcineurin/NFAT signaling pathway. Mol Cell Biochem. 2008;317:189–96.

    PubMed  CAS  Google Scholar 

  48. Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368:1096–105.

    PubMed  CAS  Google Scholar 

  49. Razeghi P, Wang ME, Youker KA, et al. Lack of NF-kappaB1 (p105/p50) attenuates unloading-induced downregulation of PPARalpha and PPARalpha-regulated gene expression in rodent heart. Cardiovasc Res. 2007;74:133–9.

    PubMed  CAS  Google Scholar 

  50. Eisner V, Criollo A, Quiroga C, et al. Hyperosmotic stress-dependent NFkappaB activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes. FEBS Lett. 2006;580:4495–500.

    PubMed  CAS  Google Scholar 

  51. Monnier L, Mas E, Ginet C, et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006;295:1681–7.

    PubMed  CAS  Google Scholar 

  52. Houstis N, Rosen ED, Lander ES. Reactive oxygen species have a causal role in multiple forms of insulin resistance. Nature. 2006;440:944–8.

    PubMed  CAS  Google Scholar 

  53. Yamamoto K, Ohki R, Lee RT, et al. Peroxisome proliferator-activated receptor gamma activators inhibit cardiac hypertrophy in cardiac myocytes. Circulation. 2001;104:1670–5.

    PubMed  CAS  Google Scholar 

  54. Sheng L, Ye P, Liu YX, et al. Peroxisome proliferator-activated receptor beta/delta activation improves angiotensin II-induced cardiac hypertrophy in vitro. Clin Exp Hypertens. 2008;30:109–19.

    PubMed  CAS  Google Scholar 

  55. Finck BN, Bernal-Mizrachi C, Han DH, et al. A potential link between muscle peroxisome proliferator-activated receptor-alpha signaling and obesity-related diabetes. Cell Metab. 2005;1:133–44.

    PubMed  CAS  Google Scholar 

  56. Lin J, Wu H, Tarr PT, et al. Transcriptional co-­activator PGC-1 alpha drives the formation of slow-twitch muscle fibres. Nature. 2002;418:797–801.

    PubMed  CAS  Google Scholar 

  57. Russell LK, Mansfield CM, Lehman JJ, et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res. 2004;94:525–33.

    PubMed  CAS  Google Scholar 

  58. Kayar SR, Conley KE, Claassen H, et al. Capillarity and mitochondrial distribution in rat myocardium following exercise training. J Exp Biol. 1986;120:189–99.

    PubMed  CAS  Google Scholar 

  59. Kemi OJ, Hoydal MA, Haram PM, et al. Exercise training restores aerobic capacity and energy transfer systems in heart failure treated with losartan. Cardiovasc Res. 2007;76:91–9.

    PubMed  CAS  Google Scholar 

  60. Murakami T, Shimomura Y, Fujitsuka N, et al. Differential adaptation to endurance training between heart and gastrocnemius muscle mitochondria in rats. Biochem Mol Biol Int. 1995;36:285–90.

    PubMed  CAS  Google Scholar 

  61. Terblanche SE, Gohil K, Packer L, et al. The effects of endurance training and exhaustive exercise on mitochondrial enzymes in tissues of the rat (Rattus norvegicus). Comp Biochem Physiol A Mol Integr Physiol. 2001;128:889–96.

    PubMed  CAS  Google Scholar 

  62. Coleman R, Weiss A, Finkelbrand S, et al. Age and exercise-related changes in myocardial mitochondria in mice. Acta Histochem. 1988;83:81–90.

    PubMed  CAS  Google Scholar 

  63. Iemitsu M, Miyauchi T, Maeda S, et al. Cardiac hypertrophy by hypertension and exercise training exhibits different gene expression of enzymes in energy metabolism. Hypertens Res. 2003;26:829–37.

    PubMed  CAS  Google Scholar 

  64. Kuo WW, Chu CY, Wu CH, et al. The profile of cardiac cytochrome c oxidase (COX) expression in an accelerated cardiac-hypertrophy model. J Biomed Sci. 2005;12:601–10.

    PubMed  CAS  Google Scholar 

  65. Stuewe SR, Gwirtz PA, Agarwal N, et al. Exercise training enhances glycolytic and oxidative enzymes in canine ventricular myocardium. J Mol Cell Cardiol. 2000;32:903–13.

    PubMed  CAS  Google Scholar 

  66. Wagner RA, Tabibiazar R, Powers J, et al. Genome-wide expression profiling of a cardiac pressure overload model identifies major metabolic and signaling pathway responses. J Mol Cell Cardiol. 2004;37:1159–70.

    PubMed  CAS  Google Scholar 

  67. Sano M, Izumi Y, Helenius K, et al. Menage-a-trois 1 is critical for the transcriptional function of PPARgamma coactivator 1. Cell Metab. 2007;5:129–42.

    PubMed  CAS  Google Scholar 

  68. De Sousa E, Veksler V, Bigard X, et al. Heart failure affects mitochondrial but not myofibrillar intrinsic properties of skeletal muscle. Circulation. 2000;102:1847–53.

    PubMed  Google Scholar 

  69. Garnier A, Fortin D, Delomenie C, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol. 2003;551:491–501.

    PubMed  CAS  Google Scholar 

  70. Javadov S, Huang C, Kirshenbaum L, et al. NHE-1 inhibition improves impaired mitochondrial permeability transition and respiratory function during postinfarction remodelling in the rat. J Mol Cell Cardiol. 2005;38:135–43.

    PubMed  CAS  Google Scholar 

  71. Jullig M, Hickey AJ, Chai CC, et al. Is the failing heart out of fuel or a worn engine running rich? A study of mitochondria in old spontaneously hypertensive rats. Proteomics. 2008;8:2556–72.

    PubMed  CAS  Google Scholar 

  72. Marin-Garcia J, Goldenthal MJ, Moe GW. Abnormal cardiac and skeletal muscle mitochondrial function in pacing-induced cardiac failure. Cardiovasc Res. 2001;52:103–10.

    PubMed  CAS  Google Scholar 

  73. Sharov VG, Goussev A, Lesch M, et al. Abnormal mitochondrial function in myocardium of dogs with chronic heart failure. J Mol Cell Cardiol. 1998;30:1757–62.

    PubMed  CAS  Google Scholar 

  74. Mettauer B, Zoll J, Garnier A, et al. Heart failure: a model of cardiac and skeletal muscle energetic failure. Pflugers Arch. 2006;452:653–66.

    PubMed  CAS  Google Scholar 

  75. Sharov VG, Todor AV, Silverman N, et al. Abnormal mitochondrial respiration in failed human myocardium. J Mol Cell Cardiol. 2000;32:2361–7.

    PubMed  CAS  Google Scholar 

  76. Sun CK, Chang LT, Sheu JJ, et al. Losartan preserves integrity of cardiac gap junctions and PGC-1 alpha gene expression and prevents cellular apoptosis in remote area of left ventricular myocardium following acute myocardial infarction. Int Heart J. 2007;48:533–46.

    PubMed  CAS  Google Scholar 

  77. Watson PA, Reusch JE, McCune SA, et al. Restoration of CREB function is linked to completion and stabilization of adaptive cardiac hypertrophy in response to exercise. Am J Physiol Heart Circ Physiol. 2007;293:H246–59.

    PubMed  CAS  Google Scholar 

  78. Witt H, Schubert C, Jaekel J, et al. Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med. 2008;86:1013–24.

    PubMed  Google Scholar 

  79. Sebastiani M, Giordano C, Nediani C, et al. Induc­tion of mitochondrial biogenesis is a maladaptive mechanism in mitochondrial cardiomyopathies. J Am Coll Cardiol. 2007;50:1362–9.

    PubMed  CAS  Google Scholar 

  80. Lehman JJ, Boudina S, Banke NH, et al. The transcriptional coactivator PGC-1alpha is essential for maximal and efficient cardiac mitochondrial fatty acid oxidation and lipid homeostasis. Am J Physiol Heart Circ Physiol. 2008;295:H185–96.

    PubMed  CAS  Google Scholar 

  81. Leone TC, Lehman JJ, Finck BN, et al. PGC-1alpha deficiency causes multi-system energy metabolic derangements: muscle dysfunction, abnormal weight control and hepatic steatosis. PLoS Biol. 2005;3:e101.

    PubMed  Google Scholar 

  82. Kim J, Wende AR, Sena S, et al. Insulin-like growth factor I receptor signaling is required for exercise-induced cardiac hypertrophy. Mol Endocrinol. 2008;22:2531–43.

    PubMed  CAS  Google Scholar 

  83. Guarente L, Picard F. Calorie restriction – the SIR2 connection. Cell. 2005;120:473–82.

    PubMed  CAS  Google Scholar 

  84. Shinmura K, Tamaki K, Bolli R. Impact of 6-mo caloric restriction on myocardial ischemic tolerance: possible involvement of nitric oxide-dependent increase in nuclear Sirt1. Am J Physiol Heart Circ Physiol. 2008;295:H2348–55.

    PubMed  CAS  Google Scholar 

  85. Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007;100:1512–21.

    PubMed  CAS  Google Scholar 

  86. Rodgers JT, Lerin C, Gerhart-Hines Z, et al. Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways. FEBS Lett. 2008;582:46–53.

    PubMed  CAS  Google Scholar 

  87. Seya K, Kanemaru K, Sugimoto C, et al. Oppo­site effects of two resveratrol (trans-3,5,4′-trihydroxystilbene) tetramers, vitisin A and hopeaphenol, on apoptosis of myocytes isolated from adult rat heart. J Pharmacol Exp Ther. 2009;328:90–8.

    PubMed  CAS  Google Scholar 

  88. Ray PS, Maulik G, Cordis GA, et al. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury. Free Radic Biol Med. 1999;27:160–9.

    PubMed  CAS  Google Scholar 

  89. Juric D, Wojciechowski P, Das DK, et al. Prevention of concentric hypertrophy and diastolic impairment in aortic-banded rats treated with resveratrol. Am J Physiol Heart Circ Physiol. 2007;292:H2138–43.

    PubMed  CAS  Google Scholar 

  90. Bertelli AA, Giovannini L, Giannessi D, et al. Antiplatelet activity of synthetic and natural resveratrol in red wine. Int J Tissue React. 1995;17:1–3.

    PubMed  CAS  Google Scholar 

  91. Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: evidence, mechanisms, and therapeutic implications. Endocr Rev. 2004;25:543–67.

    PubMed  CAS  Google Scholar 

  92. Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1–21.

    PubMed  CAS  Google Scholar 

  93. Wold LE, Ceylan-Isik AF, Ren J. Oxidative stress and stress signaling: menace of diabetic cardiomyopathy. Acta Pharmacol Sin. 2005;26:908–17.

    PubMed  CAS  Google Scholar 

  94. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001;414:813–20.

    PubMed  CAS  Google Scholar 

  95. Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318:1315–21.

    PubMed  CAS  Google Scholar 

  96. Koya D, King GL. Protein kinase C activation and the development of diabetic complications. Diabetes. 1998;47:859–66.

    PubMed  CAS  Google Scholar 

  97. Keogh RJ, Dunlop ME, Larkins RG. Effect of inhibition of aldose reductase on glucose flux, diacylglycerol formation, protein kinase C, and phospholipase A2 activation. Metabolism. 1997;46:41–7.

    PubMed  CAS  Google Scholar 

  98. Jiang T, Che Q, Lin Y, et al. Aldose reductase regulates TGF-beta1-induced production of fibronectin and type IV collagen in cultured rat mesangial cells. Nephrology (Carlton). 2006;11:105–12.

    CAS  Google Scholar 

  99. Sack MN. Type 2 diabetes, mitochondrial biology and the heart. J Mol Cell Cardiol. 2009;46:842–9.

    PubMed  CAS  Google Scholar 

  100. Liu SS. Generating, partitioning, targeting and functioning of superoxide in mitochondria. Biosci Rep. 1997;17:259–72.

    PubMed  CAS  Google Scholar 

  101. Teshima Y, Akao M, Jones SP, et al. Uncoupling protein-2 overexpression inhibits mitochondrial death pathway in cardiomyocytes. Circ Res. 2003;93:192–200.

    PubMed  CAS  Google Scholar 

  102. Laskowski KR, Russell 3rd RR. Uncoupling proteins in heart failure. Curr Heart Fail Rep. 2008;5:75–9.

    PubMed  CAS  Google Scholar 

  103. Djouadi F, Brandt JM, Weinheimer CJ, et al. The role of the peroxisome proliferator-activated receptor alpha (PPAR alpha) in the control of cardiac lipid metabolism. Prostaglandins Leukot Essent Fatty Acids. 1999;60:339–43.

    PubMed  CAS  Google Scholar 

  104. Brandt JM, Djouadi F, Kelly DP. Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem. 1998;273:23786–92.

    PubMed  CAS  Google Scholar 

  105. Finck BN, Lehman JJ, Leone TC, et al. The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest. 2002;109:121–30.

    PubMed  CAS  Google Scholar 

  106. Yang J, Sambandam N, Han X, et al. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res. 2007;100:1208–17.

    PubMed  CAS  Google Scholar 

  107. Chiu HC, Kovacs A, Blanton RM, et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res. 2005;96:225–33.

    PubMed  CAS  Google Scholar 

  108. Zhao G, Jeoung NH, Burgess SC, et al. Overexpression of pyruvate dehydrogenase kinase 4 in heart perturbs metabolism and exacerbates calcineurin-induced cardiomyopathy. Am J Physiol Heart Circ Physiol. 2008;294:H936–43.

    PubMed  CAS  Google Scholar 

  109. Sharma V, Dhillon P, Wambolt R, et al. Metoprolol improves cardiac function and modulates cardiac metabolism in the streptozotocin (STZ) diabetic rat. Am J Physiol Heart Circ Physiol. 2008;294:H1609–20.

    PubMed  CAS  Google Scholar 

  110. Sharma V, Dhillon P, Parsons H, et al. Metoprolol represses PGC1alpha-mediated carnitine palmitoyltransferase-1B expression in the diabetic heart. Eur J Pharmacol. 2009;607:156–66.

    PubMed  CAS  Google Scholar 

  111. Young ME, McNulty P, Taegtmeyer H. Adaptation and maladaptation of the heart in diabetes: Part II: potential mechanisms. Circulation. 2002;105:1861–70.

    PubMed  CAS  Google Scholar 

  112. Taegtmeyer H, McNulty P, Young ME. Adaptation and maladaptation of the heart in diabetes: Part I: general concepts. Circulation. 2002;105:1727–33.

    PubMed  CAS  Google Scholar 

  113. Narayanan S. Aldose reductase and its inhibition in the control of diabetic complications. Ann Clin Lab Sci. 1993;23:148–58.

    PubMed  CAS  Google Scholar 

  114. Weigert C, Brodbeck K, Lehmann R, et al. Overexpression of glutamine:fructose-6-phosphate-amidotransferase induces transforming growth factor-beta1 synthesis in NIH-3T3 fibroblasts. FEBS Lett. 2001;488:95–9.

    PubMed  CAS  Google Scholar 

  115. Burt DJ, Gruden G, Thomas SM, et al. P38 mitogen-activated protein kinase mediates hexosamine-induced TGFbeta1 mRNA expression in human mesangial cells. Diabetologia. 2003;46:531–7.

    PubMed  CAS  Google Scholar 

  116. Kolm-Litty V, Sauer U, Nerlich A, et al. High glucose-induced transforming growth factor beta1 production is mediated by the hexosamine pathway in porcine glomerular mesangial cells. J Clin Invest. 1998;101:160–9.

    PubMed  CAS  Google Scholar 

  117. Swynghedauw B, Delcayre C, Samuel JL, et al. Molecular mechanisms in evolutionary cardiology failure. Ann NY Acad Sci. 2010;1188:58–67.

    PubMed  CAS  Google Scholar 

  118. Kassiotis C, Rajabi M, Taegtmeyer H. Metabolic reserve of the heart: the forgotten link between contraction and coronary flow. Prog Cardiovasc Dis. 2008;51:74–88.

    PubMed  CAS  Google Scholar 

  119. Marzetti E, Wohlgemuth SE, Anton SD, et al. Cellular mechanisms of cardioprotection by calorie restriction: state of the science and future perspectives. Clin Geriatr Med. 2009;25:715–32.

    PubMed  Google Scholar 

  120. Durgan DJ, Young ME. The cardiomyocyte circadian clock: emerging roles in health and disease. Circ Res. 2010;106:647–58.

    PubMed  CAS  Google Scholar 

  121. Meng QJ, Logunova L, Maywood ES, et al. Setting clock speed in mammals: the CK1 epsilon tau mutation in mice accelerates circadian pacemakers by selectively destabilizing PERIOD proteins. Neuron. 2008;58:78–88.

    PubMed  CAS  Google Scholar 

  122. Um JH, Yang S, Yamazaki S, et al. Activation of 5′-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem. 2007;282:20794–8.

    PubMed  CAS  Google Scholar 

  123. Bray MS, Young ME. Diurnal variations in myocardial metabolism. Cardiovasc Res. 2008;79:228–37.

    PubMed  CAS  Google Scholar 

  124. Durgan DJ, Hotze MA, Tomlin TM, et al. The intrinsic circadian clock within the cardiomyocyte. Am J Physiol Heart Circ Physiol. 2005;289:H1530–41.

    PubMed  CAS  Google Scholar 

  125. Young ME, Razeghi P, Cedars AM, et al. Intrinsic diurnal variations in cardiac metabolism and contractile function. Circ Res. 2001;89:1199–208.

    PubMed  CAS  Google Scholar 

  126. Stavinoha MA, Rayspellicy JW, Hart-Sailors ML, et al. Diurnal variations in the responsiveness of cardiac and skeletal muscle to fatty acids. Am J Physiol Endocrinol Metab. 2004;287:E878–87.

    PubMed  CAS  Google Scholar 

  127. Priestman DA, Orfali KA, Sugden MC. Pyruvate inhibition of pyruvate dehydrogenase kinase. Effects of progressive starvation and hyperthyroidism in vivo, and of dibutyryl cyclic AMP and fatty acids in cultured cardiac myocytes. FEBS Lett. 1996;393:174–8.

    PubMed  CAS  Google Scholar 

  128. Park TS, Hu Y, Noh HL, et al. Ceramide is a cardiotoxin in lipotoxic cardiomyopathy. J Lipid Res. 2008;49:2101–12.

    PubMed  CAS  Google Scholar 

  129. Bray MS, Shaw CA, Moore MW, et al. Disruption of the circadian clock within the cardiomyocyte influences myocardial contractile function, metabolism, and gene expression. Am J Physiol Heart Circ Physiol. 2008;294:H1036–47.

    PubMed  CAS  Google Scholar 

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Acknowledgements

Studies quoted from our laboratory were supported by the Canadian Institutes of Health Research (CIHR).

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Authors and Affiliations

  1. Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC, Canada

    Vijay Sharma

  2. Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, Canada

    John H. McNeill

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  1. Vijay Sharma
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  2. John H. McNeill
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Correspondence to John H. McNeill .

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Editors and Affiliations

  1. St. Boniface General Hospital, Research Centre, Institute of Cardiovascular Sciences, Tache Avenue 351, Winnipeg, R2H 2A6, Manitoba, Canada

    Naranjan S. Dhalla

  2. Jikei University School of Medicine, Shibuya-ku, Ebisu 3-31-6, Tokyo, 150-0013, Japan

    Makoto Nagano

  3. Czech Republic, Institute of Physiology, Academy of Sciences of the, Videnska 1083, Prague, 142 20, Czech Republic

    Bohuslav Ostadal

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Sharma, V., McNeill, J.H. (2011). Cardiac Dysfunction and Metabolism: Unravelling the Molecular Cross-Talk. In: Dhalla, N., Nagano, M., Ostadal, B. (eds) Molecular Defects in Cardiovascular Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7130-2_9

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  • DOI: https://doi.org/10.1007/978-1-4419-7130-2_9

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