Targeting myocardial substrate metabolism in heart failure: Potential for new therapies

European Journal of Heart Failure

Volumn 14, Issue 2, 2012, Pages 120-129

  Ardehali, Hossein ^a   Sabbah, Hani N ^b   Burke, Michael A ^a   Sarma, Satyam ^a   Liu, Peter P ^c   Cleland, John G F ^d   Maggioni, Aldo ^e   Fonarow, Gregg C ^f   Abel, E Dale ^g   Campia, Umberto ^a   Gheorghiade, Mihai ^a  

^a NORTHWESTERN UNIVERSITY   (United States)

^b HENRY FORD HEALTH SYSTEM   (United States)

^c UNIVERSITY OF TORONTO   (Canada)

^d UNIVERSITY OF HULL   (United Kingdom)

^e ANMCO RESEARCH CENTER   (Italy)

^f UNIVERSITY OF CALIFORNIA   (United States)

^g UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

Author keywords

AMP activated kinase; Cardiac metabolism; Energetics; Heart failure

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; 5 AMINO 4 IMIDAZOLECARBOXAMIDE RIBOSIDE; ACIPIMOX; ADENOSINE TRIPHOSPHATE; DICHLOROACETIC ACID; ENALAPRIL; ETOMOXIR; EXENDIN 4; FATTY ACID; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; GLUCOSE TRANSPORTER 1; GLUCOSE TRANSPORTER 4; GLYCOGEN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INSULIN; LIRAGLUTIDE; METFORMIN; METOPROLOL; PERHEXILINE; POTASSIUM; RANOLAZINE; TRIMETAZIDINE;

BRADYCARDIA; CARDIOMYOPATHY; CLINICAL TRIAL (TOPIC); CONGESTIVE CARDIOMYOPATHY; CORONARY ARTERY BYPASS GRAFT; CORONARY ARTERY DISEASE; DIABETES MELLITUS; DISEASE COURSE; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DRUG TREATMENT FAILURE; DRUG WITHDRAWAL; ENZYME ACTIVATION; FATTY ACID METABOLISM; FATTY ACID OXIDATION; FATTY ACID TRANSPORT; GENE DELETION; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLYCOGEN METABOLISM; GLYCOGEN STORAGE DISEASE; HEART FAILURE; HEART FUNCTION; HEART INFARCTION; HEART LEFT VENTRICLE EJECTION FRACTION; HEART MUSCLE INJURY; HEART MUSCLE ISCHEMIA; HEART MUSCLE METABOLISM; HEART PROTECTION; HEART VENTRICLE HYPERTROPHY; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; HYPERURICEMIA; HYPOGLYCEMIA; INSULIN RESISTANCE; INSULIN TREATMENT; LIVER FUNCTION TEST; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PERIOPERATIVE PERIOD; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; REVIEW; SIDE EFFECT; SIGNAL TRANSDUCTION; SUDDEN DEATH; TREADMILL EXERCISE; TREATMENT WITHDRAWAL;

ADULT; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; DISEASE MODELS, ANIMAL; ENERGY METABOLISM; FATTY ACIDS; GLUCOSE; HEART FAILURE; HUMANS; MICE; MYOCARDIUM; MYOCYTES, CARDIAC;

EID: 84856134386     PISSN: 13889842     EISSN: 18790844     Source Type: Journal    
DOI: 10.1093/eurjhf/hfr173     Document Type: Review

References (96)

1. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, Ferguson TB, Ford E, Furie K, Gillespie C, Go A, Greenlund K, Haase N, Hailpern S, Ho PM, Howard V, Kissela B, Kittner S, Lackland D, Lisabeth L, Marelli A, McDermott MM, Meigs J, Mozaffarian D, Mussolino M, Nichol G, Roger VL, Rosamond W, Sacco R, Sorlie P, Thom T, Wasserthiel-Smoller S, Wong ND, Wylie-Rosett J. Heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 2010;121:e46-e215.
2. Baldasseroni S, Opasich C, Gorini M, Lucci D, Marchionni N, Marini M, Campana C, Perini G, Deorsola A, Masotti G, Tavazzi L, Maggioni AP. Left bundlebranch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure. Am Heart J 2002;143:398-405. (Pubitemid 34185169)
3. Lowes BD, Gilbert EM, Abraham WT, Minobe WA, Larrabee P, Ferguson D, Wolfel EE, Lindenfeld J, Tsvetkova T, Robertson AD, Quaife RA, Bristow MR. Myocardial gene expression in dilated cardiomyopathy treated with beta-blocking agents. N Engl J Med 2002;346:1357-1365. (Pubitemid 34754608)
4. Cleland JG, Pennell DJ, Ray SG, Coats AJ, Macfarlane PW, Murray GD, Mule JD, Vered Z, Lahiri A. Myocardial viability as a determinant of the ejection fraction response to carvedilol in patients with heart failure (CHRISTMAS trial): randomised controlled trial. Lancet 2003;362:14-21. (Pubitemid 36840896)
5. Taegtmeyer H. Cardiac metabolism as a target for the treatment of heart failure. Circulation 2004;110:894-896. (Pubitemid 39128613)
6. Shen W, Vatner DE, Vatner SF, Ingwall JS. Progressive loss of creatine maintains a near normal DeltaG approximately (ATP) in transgenic mouse hearts with cardiomyopathy caused by overexpressing Gsalpha. J Mol Cell Cardiol 2010;48:591-599.
7. Randle PJ. Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. Diabetes Metab Rev 1998;14:263-283. (Pubitemid 29110250)
8. Taegtmeyer H, Harinstein ME, Gheorghiade M. More than bricks and mortar: comments on protein and amino acid metabolism in the heart. Am J Cardiol 2008;101:3E-7E.
9. Neubauer S, Horn M, Cramer M, Harre K, Newell JB, Peters W, Pabst T, Ertl G, Hahn D, Ingwall JS, Kochsiek K. Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy. Circulation 1997; 96:2190-2196. (Pubitemid 27425822)
10. Neubauer S. The failing heart-an engine out of fuel. N Engl J Med 2007;356: 1140-1151. (Pubitemid 46425598)
11. Van Bilsen M, Smeets PJ, Gilde AJ, van der Vusse GJ. Metabolic remodelling of the failing heart: the cardiac burn-out syndrome? Cardiovasc Res 2004;61:218-226. (Pubitemid 38091762)
12. Rajabi M, Kassiotis C, Razeghi P, Taegtmeyer H. Return to the fetal gene program protects the stressed heart: a strong hypothesis. Heart Fail Rev 2007;12:331-343. (Pubitemid 350176706)
13. Tang WH, Francis GS. Neurohormonal upregulation in heart failure. Heart Fail Clin 2005;1:1-9.
14. Grossman W, Jones D, McLaurin LP. Wall stress and patterns of hypertrophy in the human left ventricle. J Clin Invest 1975;56:56-64.
15. Linzbach AJ. Heart failure from the point of view of quantitative anatomy. Am J Cardiol 1960;5:370-382.
16. Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure. N Engl J Med 1999;341:1276-1283. (Pubitemid 29489744)
17. Schaefer A, Klein G, Brand B, Lippolt P, Drexler H, Meyer GP. Evaluation of left ventricular diastolic function by pulsed Doppler tissue imaging in mice. J Am Soc Echocardiogr 2003;16:1144-1149. (Pubitemid 37371658)
18. Christensen G, Chen J, Ross J, Chien KR. Mouse models of human cardiovascular disease. In: Chien KR, ed. Molecular Basis of Cardiovascular Disease: A Companion to Braunwald's Heart Disease. 2nd ed. Philadelphia: Saunders; 2004. p72-106.
19. Opie LH, Commerford PJ, Gersh BJ, Pfeffer MA. Controversies in ventricular remodelling. Lancet 2006;367:356-367. (Pubitemid 43151469)
20. Toischer K, Rokita AG, Unsöld B, Zhu W, Kararigas G, Sossalla S, Reuter SP, Becker A, Teucher N, Seidler T, Grebe C, Preuss L, Gupta SN, Schmidt K, Lehnart SE, Krüger M, Linke WA, Backs J, Regitz-Zagrosek V, Schäfer K, Field LJ, Maier LS, Hasenfuss G. Differential cardiac remodeling in preload versus afterload. Circulation 2010;122:993-1003.
21. Taegtmeyer H. Energy metabolism of the heart: from basic concepts to clinical applications. Curr Probl Cardiol 1994;19:59-113.
22. Taegtmeyer H, Overturf ML. Effects of moderate hypertension on cardiac function and metabolism in the rabbit. Hypertension 1988;11:416-426.
23. Ichihara K, Abiko Y. Inhibition of endo-and epicardial glycogenolysis by propranolol in ischemic hearts. Am J Physiol 1977;232:H349-H353.
24. Kantor PF, Robertson MA, Coe JY, Lopaschuk GD. Volume overload hypertrophy of the newborn heart slows the maturation of enzymes involved in the regulation of fatty acid metabolism. J Am Coll Cardiol 1999;33:1724-1734.
25. Morrow DA, Givertz MM. Modulation of myocardial energetics: emerging evidence for a therapeutic target in cardiovascular disease. Circulation 2005;112: 3218-3221. (Pubitemid 43739364)
26. Boehm EA, Jones BE, Radda GK, Veech RL, Clarke K. Increased uncoupling proteins and decreased efficiency in palmitate-perfused hyperthyroid rat heart. AmJ Physiol Heart Circ Physiol 2001;280:H977-H983.
27. Korvald C, Elvenes OP, Myrmel T. Myocardial substrate metabolism influences left ventricular energetics in vivo. Am J Physiol Heart Circ Physiol 2000;278: H1345-H1351. (Pubitemid 30235514)
28. Chavez PN, Stanley WC, McElfresh TA, Huang H, Sterk JP, Chandler MP. Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia. Am J Physiol Heart Circ Physiol 2003;284:H1521-H1527. (Pubitemid 36460762)
29. Abel ED. Glucose transport in the heart. Front Biosci 2004;9:201-215.
30. Eberli FR, Weinberg EO, Grice WN, Horowitz GL, Apstein CS. Protective effect of increased glycolytic substrate against systolic and diastolic dysfunction and increased coronary resistance from prolonged global underperfusion and reperfusion in isolated rabbit hearts perfused with erythrocyte suspensions. Circ Res 1991;68:466-481.
31. Domenighetti AA, Danes VR, Curl CL, Favaloro JM, Proietto J, Delbridge LM. Targeted GLUT-4 deficiency in the heart induces cardiomyocyte hypertrophy and impaired contractility linked with Ca(2+) and proton flux dysregulation. J Mol Cell Cardiol 2010;48:663-672.
32. Paternostro G, Pagano D, Gnecchi-Ruscone T, Bonser RS, Camici PG. Insulin resistance in patients with cardiac hypertrophy. Cardiovasc Res 1999;42:246-253. (Pubitemid 29167091)
33. Scheuermann-Freestone M, Madsen PL, Manners D, Blamire AM, Buckingham RE, Styles P, Radda GK, Neubauer S, Clarke K. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 2003;107: 3040-3046. (Pubitemid 36758977)
34. Nikolaidis LA, Sturzu A, Stolarski C, Elahi D, Shen YT, Shannon RP. The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy. Cardiovasc Res 2004;61:297-306. (Pubitemid 38091770)
35. Sodi-Pallares D, Testelli MR, Fishleder BL, Bisteni A, Medrano GA, Friedland C, De Micheli A. Effects of an intravenous infusion of a potassium-glucose-insulin solution on the electrocardiographic signs of myocardial infarction. A preliminary clinical report. Am J Cardiol 1962;9:166-181.
36. Sun D, Nguyen N, DeGrado TR, Schwaiger M, Brosius FC 3rd. Ischemia induces translocation of the insulin-responsive glucose transporter GLUT4 to the plasma membrane of cardiac myocytes. Circulation 1994;89:793-798. (Pubitemid 24056208)
37. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ 1997;314:1512-1515. (Pubitemid 27216066)
38. Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, Efendic S, Fisher M, Hamsten A, Herlitz J, Hildebrandt P, MacLeod K, Laakso M, Torp-Pedersen C, Waldenstrom A. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 2005;26:650-661. (Pubitemid 40516876)
39. Ban K, Noyan-Ashraf MH, Hoefer J, Bolz SS, Drucker DJ, Husain M. Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and-independent pathways. Circulation 2008;117:2340-2350. (Pubitemid 351653542)
40. Bhashyam S, Fields AV, Patterson B, Testani JM, Chen L, Shen YT, Shannon RP. Glucagon-like peptide-1 increases myocardial glucose uptake via pp38alpha MAP kinase-mediated, nitric oxide-dependent mechanisms in conscious dogs with dilated cardiomyopathy. Circ Heart Fail 2010;3:512-521.
41. Nikolaidis LA, Elahi D, Hentosz T, Doverspike A, Huerbin R, Zourelias L, Stolarski C, Shen YT, Shannon RP. Recombinant glucagon-like peptide-1 increases myocardial glucose uptake and improves left ventricular performance in conscious dogs with pacing-induced dilated cardiomyopathy. Circulation 2004;110: 955-961. (Pubitemid 39128621)
42. Bersin RM, Stacpoole PW. Dichloroacetate as metabolic therapy for myocardial ischemia and failure. Am Heart J 1997;134:841-855. (Pubitemid 27522989)
43. Di Napoli P, Taccardi AA, Barsotti A. Long term cardioprotective action of trimetazidine and potential effect on the inflammatory process in patients with ischaemic dilated cardiomyopathy. Heart 2005;91:161-165.
44. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005;85:1093-1129. (Pubitemid 40894649)
45. Bessman SP, Geiger PJ. Transport of energy in muscle: the phosphorylcreatine shuttle. Science 1981;211:448-452. (Pubitemid 11145312)
46. Frayn KN, Arner P, Yki-Jarvinen H. Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem 2006;42:89-103.
47. Mjos OD. Effect of free fatty acids on myocardial function and oxygen consumption in intact dogs. J Clin Invest 1971;50:1386-1389.
48. Hinkle PC. P/O ratios of mitochondrial oxidative phosphorylation. Biochim Biophys Acta 2005;1706:1-11. (Pubitemid 40037758)
49. Cline GW, Vidal-Puig AJ, Dufour S, Cadman KS, Lowell BB, Shulman GI. In vivo effects of uncoupling protein-3 gene disruption on mitochondrial energy metabolism. J Biol Chem 2001;276:20240-20244.
50. Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010;90:207-258.
51. Witteles RM, Fowler MB. Insulin-resistant cardiomyopathy clinical evidence, mechanisms, and treatment options. J Am Coll Cardiol 2008;51:93-102.
52. Opie LH, Knuuti J. The adrenergic-fatty acid load in heart failure. J Am Coll Cardiol 2009;54:1637-1646.
53. Tuunanen H, Engblom E, Naum A, Scheinin M, Nagren K, Airaksinen J, Nuutila P, Iozzo P, Ukkonen H, Knuuti J. 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 2006;12:644-652. (Pubitemid 44512144)
54. Lee L, Campbell R, Scheuermann-Freestone M, Taylor R, Gunaruwan P, Williams L, Ashrafian H, Horowitz J, Fraser AG, Clarke K, Frenneaux M. Metabolic modulation with perhexiline in chronic heart failure: a randomized, controlled trial of short-term use of a novel treatment. Circulation 2005;112:3280-3288. (Pubitemid 43739373)
55. McGarry JD, Brown NF. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem 1997;244:1-14. (Pubitemid 27079689)
56. 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 1988;63:1036-1043. (Pubitemid 19004258)
57. Selby PL, Sherratt HS. Substituted 2-oxiranecarboxylic acids: a new group of candidate hypoglycaemic drugs. Trends Pharmacol Sci 1989;10:495-500. (Pubitemid 19285629)
58. Paulson DJ, Noonan JJ, Ward KM, Stanley H, Sherratt A, Shug AL. Effects of POCA on metabolism and function in the ischemic rat heart. Basic Res Cardiol 1986;81:180-187. (Pubitemid 16111893)
59. Vetter R, Rupp H. CPT-1 inhibition by etomoxir has a chamber-related action on cardiac sarcoplasmic reticulum and isomyosins. Am J Physiol 1994;267: H2091-H2099.
60. Schmidt-Schweda S, Holubarsch C. First clinical trial with etomoxir in patients with chronic congestive heart failure. Clin Sci (Lond) 2000;99:27-35. (Pubitemid 30479390)
61. Holubarsch CJ, Rohrbach M, Karrasch M, Boehm E, Polonski L, Ponikowski P, Rhein S. A double-blind randomized multicentre clinical trial to evaluate the efficacy and safety of two doses of etomoxir in comparison with placebo in patients with moderate congestive heart failure: the ERGO (etomoxir for the recovery of glucose oxidation) study. Clin Sci (Lond) 2007;113:205-212. (Pubitemid 47237917)
62. Kennedy JA, Kiosoglous AJ, Murphy GA, Pelle MA, Horowitz JD. Effect of perhexiline and oxfenicine on myocardial function and metabolism during low-flow ischemia/reperfusion in the isolated rat heart. J Cardiovasc Pharmacol 2000;36:794-801.
63. 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 2003; 93:e33-e37.
64. Renaud JF. Internal pH, Na+, and Ca2+ regulation by trimetazidine during cardiac cell acidosis. Cardiovasc Drugs Ther 1988;1:677-686.
65. Kiyosue T, Nakamura S, Arita M. Effects of trimetazidine on action potentials and membrane currents of guinea-pig ventricular myocytes. J Mol Cell Cardiol 1986;18: 1301-1311. (Pubitemid 17228948)
66. Meng D, Feng L, Chen XJ, Yang D, Zhang JN. Trimetazidine improved Ca2+ handling in isoprenaline-mediated myocardial injury of rats. Exp Physiol 2006;91: 591-601.
67. Kohlhaas M, Maack C. Adverse bioenergetic consequences of Na+-Ca2+ exchanger-mediated Ca2+ influx in cardiac myocytes. Circulation 2010;122: 2273-2280.
68. Fragasso G, Palloshi A, Puccetti P, Silipigni C, Rossodivita A, Pala M, Calori G, Alfieri O, Margonato A. A randomized clinical trial of trimetazidine, a partial free fatty acid oxidation inhibitor, in patients with heart failure. J Am Coll Cardiol 2006;48:992-998. (Pubitemid 44292461)
69. Scirica BM, Morrow DA. Ranolazine in patients with angina and coronary artery disease. Curr Cardiol Rep 2007;9:272-278. (Pubitemid 47072824)
70. McCormack JG, Barr RL,Wolff AA, Lopaschuk GD. Ranolazine stimulates glucose oxidation in normoxic, ischemic, and reperfused ischemic rat hearts. Circulation 1996;93:135-142. (Pubitemid 26007542)
71. Antzelevitch C, Belardinelli L, Zygmunt AC, Burashnikov A, Di Diego JM, Fish JM, Cordeiro JM, Thomas G. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004;110:904-910. (Pubitemid 39136212)
72. Belardinelli L, Shryock JC, Fraser H. Inhibition of the late sodium current as a potential cardioprotective principle: effects of the late sodium current inhibitor ranolazine. Heart 2006;92 Suppl 4:iv6-iv14. (Pubitemid 43974036)
73. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, Murphy SA, Budaj A, Varshavsky S,Wolff AA, Skene A, McCabe CH, Braunwald E. Effects of ranolazine on recurrent cardiovascular events in patients with non-ST-elevation acute coronary syndromes: the MERLIN-TIMI 36 randomized trial. JAMA 2007;297: 1775-1783. (Pubitemid 46658646)
74. Liu B, Clanachan AS, Schulz R, Lopaschuk GD. Cardiac efficiency is improved after ischemia by altering both the source and fate of protons. Circ Res 1996;79: 940-948. (Pubitemid 26359235)
75. Wargovich TJ, MacDonald RG, Hill JA, Feldman RL, Stacpoole PW, Pepine CJ. Myocardial metabolic and hemodynamic effects of dichloroacetate in coronary artery disease. Am J Cardiol 1988;61:65-70.
76. Lopaschuk GD, Stanley WC. Malonyl-CoA decarboxylase inhibition as a novel approach to treat ischemic heart disease. Cardiovasc Drugs Ther 2006;20:433-439. (Pubitemid 46144220)
77. Tuunanen H, Engblom E, Naum A, Nagren K, Hesse B, Airaksinen KE, Nuutila P, Iozzo P, Ukkonen H, Opie LH, Knuuti J. Free fatty acid depletion acutely decreases cardiac work and efficiency in cardiomyopathic heart failure. Circulation 2006;114:2130-2137. (Pubitemid 44747893)
78. Ingwall JS, Shen W. On energy circuits in the failing myocardium. Eur J Heart Fail 2010;12:1268-1270.
79. Aksentijevic D, Lygate CA, Makinen K, Zervou S, Sebag-Montefiore L, Medway D, Barnes H, Schneider JE, Neubauer S. High-energy phosphotransfer in the failing mouse heart: role of adenylate kinase and glycolytic enzymes. Eur J Heart Fail 2010;12:1282-1289.
80. Dyck JR, Lopaschuk GD. AMPK alterations in cardiac physiology and pathology: enemy or ally? J Physiol 2006;574:95-112. (Pubitemid 43905800)
81. Fisslthaler B, Fleming I. Activation and signaling by the AMP-activated protein kinase in endothelial cells. Circ Res 2009;105:114-127.
82. Hardie DG. Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. FEBS Lett 2008;582:81-89. (Pubitemid 350297243)
83. Ruderman NB, Cacicedo JM, Itani S, Yagihashi N, Saha AK, Ye JM, Chen K, Zou M, Carling D, Boden G, Cohen RA, Keaney J, Kraegen EW, Ido Y. Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem Soc Trans 2003;31: 202-206. (Pubitemid 36241428)
84. Lopaschuk GD. AMP-activated protein kinase control of energy metabolism in the ischemic heart. Int J Obes (Lond) 2008;32 Suppl 4:S29-S35.
85. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res 2009;81:412-419.
86. Tian R, Musi N, D'Agostino J, Hirshman MF, Goodyear LJ. Increased adenosine monophosphate-activated protein kinase activity in rat hearts with pressure-overload hypertrophy. Circulation 2001;104:1664-1669. (Pubitemid 32947531)
87. Arad M, Benson DW, Perez-Atayde AR, McKenna WJ, Sparks EA, Kanter RJ, McGarry K, Seidman JG, Seidman CE. Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 2002;109:357-362. (Pubitemid 34141809)
88. Blair E, Redwood C, Ashrafian H, Oliveira M, Broxholme J, Kerr B, Salmon A, Ostman-Smith I, Watkins H. Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 2001;10:1215-1220. (Pubitemid 32487544)
89. Ahmad F, Arad M, Musi N, He H, Wolf C, Branco D, Perez-Atayde AR, Stapleton D, Bali D, Xing Y, Tian R, Goodyear LJ, Berul CI, Ingwall JS, Seidman CE, Seidman JG. Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy. Circulation 2005;112:3140-3148.
90. Zou L, Shen M, Arad M, He H, Lofgren B, Ingwall JS, Seidman CE, Seidman JG, Tian R. N488I mutation of the gamma2-subunit results in bidirectional changes in AMP-activated protein kinase activity. Circ Res 2005;97:323-328. (Pubitemid 41216136)
91. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-1174. (Pubitemid 32995375)
92. Gundewar S, Calvert JW, Jha S, Toedt-Pingel I, Ji SY, Nunez D, Ramachandran A, Anaya-Cisneros M, Tian R, Lefer DJ. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res 2009;104:403-411.
93. Sasaki H, Asanuma H, Fujita M, Takahama H, Wakeno M, Ito S, Ogai A, Asakura M, Kim J, Minamino T, Takashima S, Sanada S, Sugimachi M, Komamura K, Mochizuki N, Kitakaze M. Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase. Circulation 2009;119: 2568-2577.
94. Ouyang J, Parakhia RA, Ochs RS. Metformin activates AMP kinase through inhibition of AMP deaminase. J Biol Chem 2011;286:1-11.
95. Saha AK, Avilucea PR, Ye JM, Assifi MM, Kraegen EW, Ruderman NB. Pioglitazone treatment activates AMP-activated protein kinase in rat liver and adipose tissue in vivo. Biochem Biophys Res Commun 2004;314:580-585. (Pubitemid 38084758)
96. Wong AK, Howie J, Petrie JR, Lang CC. AMP-activated protein kinase pathway: a potential therapeutic target in cardiometabolic disease. Clin Sci (Lond) 2009;116: 607-620.