Myocardial fatty acid utilization as a determinant of cardiac efficiency and function

Bibliography

• Bing RJ, Hammond MM, Handelsman JC et al.: The measurement of coronary blood flow, oxygen consumption, and efficiency of the left ventricle in man. Am. Heart J. 38, 1–24 (1949).
   Google Scholar
• Stanley WC, Recchia FA, Lopaschuk GD: Myocardial substrate metabolism in the normal and failing heart. Physiol. Rev. 85, 1093–1129 (2005)
   Google Scholar
• Suga H: Ventricular energetics. Physiol. Rev. 70, 247–277 (1990)
   Google Scholar
• Suga H: Cardiac energetics: from E(max) to pressure–volume area. Clin. Exp. Pharmacol. Physiol. 30, 580–585 (2003)
   Google Scholar
• Knaapen P, Germans T, Knuuti J et al.: Myocardial energetics and efficiency: current status of the noninvasive approach. Circulation 115, 918–927 (2007)
   Google Scholar
• How OJ, Aasum E, Larsen TS: Workindependent assessment of efficiency in ex vivo working rodent hearts within the PVA-MVO2 framework. Acta Physiol. 190, 171–175 (2007)
   Google Scholar
• Aasum E, Hafstad AD, Severson DL, Larsen TS: Age-dependent changes in metabolism, contractile function, and ischemic sensitivity in hearts from db/db mice. Diabetes 52, 434–441 (2003)
   Google Scholar
• Mazumder PK, O’Neill BT, Roberts MW et al.: Impaired cardiac efficiency and increased fatty acid oxidation in insulinresistant ob/ob mouse hearts. Diabetes 53, 2366–2374 (2004)
   Google Scholar
• Carley AN, Severson DL: Fatty acid metabolism is enhanced in Type 2 diabetic hearts. Biochim. Biophys. Acta 1734, 112–126 (2005)
   Google Scholar
• Carroll R, Carley AN, Dyck JR, Severson DL: Metabolic effects of insulin on cardiomyocytes from control and diabetic db/db mouse hearts. Am. J. Physiol. Endocrinol. Metab. 288, E900–E906 (2005)
   Google Scholar
• Wang P, Lloyd SG, Zeng H, Bonen A, Chatham JC: Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats. Am. J. Physiol. Heart Circ. Physiol. 288, H2102–H2110 (2005)
   Google Scholar
• Peterson LR, Herrero P, Schechtman KBet al.: Effect of obesity and insulin resistance on myocardial substrate metabolism and efficiency in young women. Circulation 109, 2191–2196 (2004)
   Google Scholar
• Buchanan J, Mazumder PK, Hu P et al.: Reduced cardiac efficiency and altered substrate metabolism precedes the onset of hyperglycemia and contractile dysfunction in two mouse models of insulin resistance and obesity. Endocrinology 146, 5341–5349 (2005)
   Google Scholar
• Aasum E, Belke DD, Severson DL et al.: Cardiac function and metabolism in Type 2 diabetic mice after treatment with BM 17.0744, a novel PPAR-a activator.Am. J. Physiol. Heart Circ. Physiol. 283,H949–H957 (2002)
   Google Scholar
• Belke DD, Larsen TS, Gibbs EM, Severson DL: Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am. J. Physiol. Endocrinol. Metab. 279, E1104–E1113 (2000)
   Google Scholar
• Suga H: Total mechanical energy of a ventricle model and cardiac oxygen consumption. Am. J. Physiol. 236, H498–H505 (1979)
   Google Scholar
• Wolff AA, Rotmensch HH, Stanley WC, Ferrari R: Metabolic approaches to the treatment of ischemic heart disease: the clinicians’ perspective. Heart Fail. Rev. 7, 187–203 (2002)
   Google Scholar
• Hinkle PC: P/O ratios of mitochondrial oxidative phosphorylation. Biochim. Biophys. Acta 1706, 1–11 (2005).
   Google Scholar
• Kadenbach B: Intrinsic and extrinsic uncoupling of oxidative phosphorylation. Biochim. Biophys. Acta 1604, 77–94 (2003)
   Google Scholar
• Nicholls DG, Bernson VS, Heaton GM: The identification of the component in the inner membrane of brown adipose tissue mitochondria responsible for regulating energy dissipation. Experientia Suppl. 32, 89–93 (1978)
   Google Scholar
• Rousset S, Alves-Guerra MC, Mozo J et al.: The biology of mitochondrial uncoupling proteins. Diabetes 53(Suppl. 1), S130–S135 (2004)
   Google Scholar
• Schrauwen P, Hesselink M: UCP2 and UCP3 in muscle controlling body metabolism. J. Exp. Biol. 205, 2275–2285 (2002).
   Google Scholar
• Hidaka S, Kakuma T, Yoshimatsu H et al.: Streptozotocin treatment upregulatesuncoupling protein 3 expression in the rat heart. Diabetes 48, 430–435 (1999)
   Google Scholar
• Boehm EA, Jones BE, Radda GK, Veech RL, Clarke K: Increased uncoupling proteins and decreased efficiency in palmitate-perfused hyperthyroid rat heart. Am. J. Physiol. Heart Circ. Physiol. 280, H977–H983 (2001).
   Google Scholar
• Murray AJ, Anderson RE, Watson GC, Radda GK, Clarke K: Uncoupling proteins in human heart. Lancet 364, 1786–1788 (2004)
   Google Scholar
• Murray AJ, Cole MA, Lygate CA et al.: Increased mitochondrial uncoupling proteins, respiratory uncoupling and decreased efficiency in the chronically infarcted rat heart. J. Mol. Cell. Cardiol. 44, 694–700 (2008)
   Google Scholar
• Boudina S, Sena S, Theobald H et al.: Mitochondrial energetics in the heart in obesity-related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 56, 2457–2466 (2007)
   Google Scholar
• Boudina S, Sena S, O’Neill BT et al.: Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112, 2686–2695 (2005)
   Google Scholar
• How OJ, Aasum E, Severson DL et al.: Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes 55, 466–473 (2006)
   Google Scholar
• Hafstad AD, Khalid AM, How OJ, Larsen TS, Aasum E: Glucose and insulin improve cardiac efficiency and postischemic functional recovery in perfused hearts from Type 2 diabetic (db/db) mice. Am. J. Physiol. Endocrinol. Metab. 292, E1288–E1294 (2007)
   Google Scholar
• Boudina S, Abel ED: Mitochondrial uncoupling: a key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda) 21, 250–258 (2006)
   Google Scholar
• Ricquier D, Bouillaud F: The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem. J. 345(Pt 2), 161–179 (2000)
   Google Scholar
• Boss O, Hagen T, Lowell BB: Uncoupling proteins 2 and 3: potential regulators of mitochondrial energy metabolism. Diabetes 49, 143–156 (2000)
   Google Scholar
• Weigle DS, Selfridge LE, Schwartz MW et al.: Elevated free fatty acids induce uncoupling protein 3 expression in muscle: a potential explanation for the effect of fasting. Diabetes 47, 298–302 (1998)
   Google Scholar
• Khalfallah Y, Fages S, Laville M, Langin D, Vidal H: Regulation of uncoupling protein-2 and uncoupling protein-3 mRNA expression during lipid infusion in human skeletal muscle and subcutaneous adipose tissue. Diabetes 49, 25–31 (2000)
   Google Scholar
• Echtay KS, Murphy MP, Smith RA, Talbot DA, Brand MD: Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants. J. Biol. Chem. 277, 47129–47135 (2002)
   Google Scholar
• Echtay KS, Roussel D, St-Pierre J et al.: Superoxide activates mitochondrial uncoupling proteins. Nature 415, 96–99 (2002)
   Google Scholar
• Murphy MP, Echtay KS, Blaikie FH et al.: Superoxide activates uncoupling proteins by generating carbon-centered radicals and initiating lipid peroxidation: studies using a mitochondria-targeted spin trap derived from a-phenyl-N-tert-butylnitrone. J. Biol. Chem. 278, 48534–48545 (2003)
   Google Scholar
• Seifert EL, Bezaire V, Estey C, Harper ME: Essential role for uncoupling protein-3 in mitochondrial adaptation to fasting but not in fatty acid oxidation or fatty acid anion export. J. Biol. Chem. 283, 25124–25131 (2008)
   Google Scholar
• Hunt MC, Alexson SE: The role acyl-CoA thioesterases play in mediating intracellular lipid metabolism. Prog. Lipid Res. 41, 99–130 (2002)
   Google Scholar
• Himms-Hagen J, Harper ME: Physiological role of UCP3 may be export of fatty acids from mitochondria when fatty acid oxidation predominates: an hypothesis. Exp. Biol. Med.(Maywood) 226, 78–84 (2001)
   Google Scholar
• Saddik M, Lopaschuk GD: Myocardial triglyceride turnover during reperfusion of isolated rat hearts subjected to a transient period of global ischemia. J. Biol. Chem. 267, 3825–3831 (1992)
   Google Scholar
• Myrmel T, Forsdahl K, Larsen TS: Triacylglycerol metabolism in hypoxic, glucose-deprived rat cardiomyocytes. J. Mol. Cell. Cardiol. 24, 855–868 (1992)
   Google Scholar
• Kourie JI: Interaction of reactive oxygen species with ion transport mechanisms. Am. J. Physiol. 275, C1–C24 (1998)
   Google Scholar
• Bolli R, Marban E: Molecular and cellular mechanisms of myocardial stunning. Physiol. Rev. 79, 609–634 (1999).
   Google Scholar
• Bers DM, Barry WH, Despa S: Intracellular Na+ regulation in cardiac myocytes. Cardiovasc. Res. 57, 897–912 (2003)
   Google Scholar
• Blaustein MP, Lederer WJ: Sodium/calcium exchange: its physiological implications. Physiol. Rev. 79, 763–854 (1999)
   Google Scholar
• Clanachan AS: Contribution of protons to post-ischemic Na+ and Ca2+ overload and left ventricular mechanical dysfunction. J. Cardiovasc. Electrophysiol. 17(Suppl. 1), S141–S148 (2006)
   Google Scholar
• Liu Q, Docherty JC, Rendell JC, Clanachan AS, Lopaschuk GD: High levels of fatty acids delay the recovery of intracellular pH and cardiac efficiency in post-ischemic hearts by inhibiting glucose oxidation. J. Am. Coll. Cardiol. 39, 718–725 (2002)
   Google Scholar
• Hool LC: What cardiologists should know about calcium ion channels and their regulation by reactive oxygen species. Heart Lung Circ. 16, 361–372 (2007)
   Google Scholar
• Rowe GT, Manson NH, Caplan M, Hess ML: Hydrogen peroxide and hydroxyl radical mediation of activated leukocyte depression of cardiac sarcoplasmic reticulum. Participation of the cyclooxygenase pathway. Circ. Res. 53, 584–591 (1983)
   Google Scholar
• Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1, 785–789 (1963)
   Google Scholar
• Randle PJ: Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab. Rev. 14, 263–283 (1998)
   Google Scholar
• Dennis SC, Gevers W, Opie LH: Protons in ischemia: where do they come from; where do they go to? J. Mol. Cell. Cardiol. 23, 1077–1086 (1991)
   Google Scholar
• Robergs RA, Ghiasvand F, Parker D: Biochemistry of exercise-induced metabolic acidosis. Am. J. Physiol. Regul. Integr. Comp. Physiol. 287, R502–R516 (2004)
   Google Scholar
• Lysiak W, Toth PP, Suelter CH, Bieber LL: Quantitation of the efflux of acylcarnitines from rat heart, brain, and liver mitochondria. J. Biol. Chem. 261, 13698–13703 (1986)
   Google Scholar
• Ussher JR, Lopaschuk GD: The malonyl CoA axis as a potential target for treating ischaemic heart disease. Cardiovasc. Res. 79, 259–268 (2008)
   Google Scholar
• Hafstad AD, Solevag GH, Severson DL, Larsen TS, Aasum E: Perfused hearts from Type 2 diabetic (db/db) mice show metabolic responsiveness to insulin. Am. J. Physiol. Heart Circ. Physiol. 290, H1763–H1769 (2006)
   Google Scholar
• Schonekess BO, Allard MF, Henning SL, Wambolt RB, Lopaschuk GD: Contribution of glycogen and exogenous glucose to glucose metabolism during ischemia in the hypertrophied rat heart. Circ. Res. 81, 540–549 (1997)
   Google Scholar
• Henning SL, Wambolt RB, Schonekess BO, Lopaschuk GD, Allard MF: Contribution of glycogen to aerobic myocardial glucose utilization. Circulation 93, 1549–1555 (1996)
   Google Scholar
• Hausenloy DJ, Yellon DM: New directions for protecting the heart against ischaemia–reperfusion injury: targeting the Reperfusion Injury Salvage Kinase (RISK)- pathway. Cardiovasc. Res. 61, 448–460 (2004)
   Google Scholar
• Lopaschuk GD, Spafford MA, Davies NJ, Wall SR: Glucose and palmitate oxidation in isolated working rat hearts reperfused after a period of transient global ischemia. Circ. Res. 66, 546–553 (1990)
   Google Scholar
• Leong HS, Grist M, Parsons H et al.: Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artifact? Am. J. Physiol. Endocrinol. Metab. 282, E1039–E1045 (2002)
   Google Scholar
• Jain M, Cui L, Brenner DA et al.: Increasedmyocardial dysfunction after ischemiareperfusion in mice lacking glucose-6- phosphate dehydrogenase. Circulation 109, 898–903 (2004).
   Google Scholar
• Jain M, Brenner DA, Cui L et al.: Glucose-6- phosphate dehydrogenase modulates cytosolic redox status and contractile phenotype in adult cardiomyocytes. Circ. Res. 93, e9–e16 (2003)
   Google Scholar
• Carley AN, Semeniuk LM, Shimoni Y et al.: Treatment of type 2 diabetic db/db mice with a novel PPARg agonist improves cardiac metabolism but not contractile function. Am. J. Physiol. Endocrinol. Metab. 286, E449–E455 (2004)
   Google Scholar
• Golfman LS, Wilson CR, Sharma S et al.: Activation of PPARg enhances myocardial glucose oxidation and improves contractile function in isolated working hearts of ZDF rats. Am. J. Physiol. Endocrinol. Metab. 289, E328–E336 (2005)
   Google Scholar
• How OJ, Larsen TS, Hafstad AD et al.: Rosiglitazone treatment improves cardiac efficiency in hearts from diabetic mice. Arch. Physiol. Biochem. 113, 211–220 (2007)
   Google Scholar
• Sidell RJ, Cole MA, Draper NJ, Desrois M, Buckingham RE, Clarke K: Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the zucker Fatty rat heart.Diabetes 51, 1110–1117 (2002)
   Google Scholar
• Jeffrey FM, Alvarez L, Diczku V, Sherry AD, Malloy CR: Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J. Cardiovasc. Pharmacol. 25, 469–472 (1995)
   Google Scholar
• Lopaschuk GD, Wall SR, Olley PM, Davies NJ: Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ. Res. 63, 1036–1043 (1988)
   Google Scholar
• Lee L, Campbell R, Scheuermann-Freestone M et al.: Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 112, 3280–3288 (2005)
   Google Scholar
• Schmidt-Schweda S, Holubarsch C: First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin. Sci. 99, 27–35 (2000)
   Google Scholar
• Lopaschuk GD, Rebeyka IM, Allard MF: Metabolic modulation: a means to mend a broken heart. Circulation 105, 140–142 (2002)
   Google Scholar
• Dyck JR, Cheng JF, Stanley WC et al.: Malonyl coenzyme A decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ. Res. 94, e78–e84 (2004)
   Google Scholar
• Dyck JR, Hopkins TA, Bonnet S et al.: Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury. Circulation 114, 1721–1728 (2006)
   Google Scholar
• Kantor PF, Lucien A, Kozak R, Lopaschuk GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. 86, 580–588 (2000)
   Google Scholar
• Lopaschuk GD, Barr R, Thomas PD, Dyck JR: Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. 93, e33–e37 (2003)
   Google Scholar
• Fragasso G, Palloshi A, Puccetti P et al.: A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J. Am. Coll. Cardiol. 48, 992–998 (2006)
   Google Scholar
• Sidell RJ, Cole MA, Draper NJ, Desrois M, Buckingham RE, Clarke K: Thiazolidinedione treatment normalizes insulin resistance and ischemic injury in the zucker Fatty rat heart. Diabetes 51, 1110–1117 (2002)
   Google Scholar
• Jeffrey FM, Alvarez L, Diczku V, Sherry AD, Malloy CR: Direct evidence that perhexiline modifies myocardial substrate utilization from fatty acids to lactate. J. Cardiovasc. Pharmacol. 25, 469–472 (1995)
   Google Scholar
• Lopaschuk GD, Wall SR, Olley PM, Davies NJ: Etomoxir, a carnitine palmitoyltransferase I inhibitor, protects hearts from fatty acid-induced ischemic injury independent of changes in long chain acylcarnitine. Circ. Res. 63, 1036–1043 (1988)
   Google Scholar
• Lee L, Campbell R, Scheuermann-Freestone M et al.: Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 112, 3280–3288 (2005)
   Google Scholar
• Schmidt-Schweda S, Holubarsch C: First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin. Sci. 99, 27–35 (2000)
   Google Scholar
• Lopaschuk GD, Rebeyka IM, Allard MF: Metabolic modulation: a means to mend a broken heart. Circulation 105, 140–142 (2002)
   Google Scholar
• Dyck JR, Cheng JF, Stanley WC et al.: Malonyl coenzyme A decarboxylase inhibition protects the ischemic heart by inhibiting fatty acid oxidation and stimulating glucose oxidation. Circ. Res. 94, e78–e84 (2004)
   Google Scholar
• Dyck JR, Hopkins TA, Bonnet S et al.: Absence of malonyl coenzyme A decarboxylase in mice increases cardiac glucose oxidation and protects the heart from ischemic injury. Circulation 114, 1721–1728 (2006)
   Google Scholar
• Kantor PF, Lucien A, Kozak R, Lopaschuk GD: The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. 86, 580–588 (2000)
   Google Scholar
• Lopaschuk GD, Barr R, Thomas PD, Dyck JR: Beneficial effects of trimetazidine in ex vivo working ischemic hearts are due to a stimulation of glucose oxidation secondary to inhibition of long-chain 3-ketoacyl coenzyme A thiolase. Circ. Res. 93, e33–e37 (2003).
   Google Scholar
• Fragasso G, Palloshi A, Puccetti P et al.: A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J. Am. Coll. Cardiol. 48, 992–998 (2006)
   Google Scholar
• Fragasso G, Perseghin G, De Cobelli F et al.: Effects of metabolic modulation by trimetazidine on left ventricular function and phosphocreatine/adenosine triphosphate ratio in patients with heart failure. Eur. Heart J. 27, 942–948 (2006)
   Google Scholar
• Tuunanen H, Engblom E, Naum A et al.: Trimetazidine, a metabolic modulator, has cardiac and extracardiac benefits in idiopathic dilated cardiomyopathy. Circulation 118, 1250–1258 (2008)
   Google Scholar
• McCormack JG, Barr RL, Wolff AA, Lopaschuk GD: Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation 93, 135–142 (1996)
   Google Scholar
• Chaitman BR, Pepine CJ, Parker JO et al.: Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized controlled trial. JAMA 291, 309–316 (2004)
   Google Scholar
• Chaitman BR, Skettino SL, Parker JO et al.: Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J. Am. Coll. Cardiol. 43, 1375–1382 (2004)
   Google Scholar
• Rousseau MF, Pouleur H, Cocco G, Wolff AA: Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am. J. Cardiol. 95, 311–316 (2005)
   Google Scholar
• Stone PH, Gratsiansky NA, Blokhin A, Huang IZ, Meng L: Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J. Am. Coll. Cardiol. 48, 566–575 (2006)
   Google Scholar
• Timmis AD, Chaitman BR, Crager M: Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur. Heart J. 27, 42–48 (2006)
   Google Scholar
• Peterson LR, Herrero P, McGill J et al.: Fatty acids and insulin modulate myocardial substrate metabolism in humans with Type 1 diabetes. Diabetes 57, 32–40 (2008)
   Google Scholar