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

Circulation Research

Volumn 86, Issue 5, 2000, Pages 580-588

  Kantor, Paul F ^a   Lucien, Arnaud ^b   Kozak, Raymond ^a   Lopaschuk, Gary D ^a  

^a UNIVERSITY OF ALBERTA   (Canada)

^b INSTITUT DE RECHERCHES INTERNATIONALES SERVIER   (France)

Author keywords

Glycolysis; Mitochondria; Trimetazidine

Indexed keywords

ACETYL COENZYME A ACYLTRANSFERASE; ANTIANGINA PECTORIS AGENT; FATTY ACID; GLUCOSE; PALMITIC ACID; PYRUVATE DEHYDROGENASE; TRIMETAZIDINE;

ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DOSE RESPONSE; ENERGY METABOLISM; ENZYME ACTIVITY; FATTY ACID OXIDATION; GLUCOSE OXIDATION; GLYCOLYSIS; HEART MITOCHONDRION; HEART MUSCLE ISCHEMIA; HEART MUSCLE METABOLISM; HEART MUSCLE OXYGEN CONSUMPTION; HEART WORK; MALE; NONHUMAN; PRIORITY JOURNAL; RAT;

EID: 0034678082     PISSN: 00097330     EISSN: None     Source Type: Journal    
DOI: 10.1161/01.RES.86.5.580     Document Type: Article

References (36)

1. Sellier P. The effects of trimetazidine on ergometric parameters in exercise-induced angina: controlled multicenter double blind versus placebo study. Arch Mal Coeur Vaiss. 1986;79:1331-1336.
2. Sellier P, Audouin P, Payen B, Duong TC, Ourbak P. Ergometric effects of a single administration of trimetazidine. Presse Med. 1986;15: 1771-1774.
3. Passeron J. Effectiveness of trimetazidine in stable effort angina due to chronic coronary insufficiency: a double-blind versus placebo study. Presse Med. 1986;15:1775-1778.
4. Gallet M. Clinical effectiveness of trimetazidine in stable effort angina: a double blind versus placebo controlled study. Presse Med. 1986;15:1779-1782.
5. Detry JM, Sellier P, Pennaforte S, Cokkinos D, Dargie H, Mathes P. Trimetazidine: a new concept in the treatment of angina: comparison with propranolol in patients with stable angina. Trimetazidine European Multicenter Study Group. Br J Clin Pharmacol. 1994;3:279-288.
6. Dalla-Volta S, Maraglino G, Della-Valentina P, Viena P, Desideri A. Comparison of trimetazidine with nifedipene in effort angina: a double-blind, crossover study. Cardiovasc Drugs Ther. 1990;4:853-859.
7. Levy S, Group of South of France Investigators. Combination therapy of trimetazidine with diltiazem in patients with coronary artery disease. Am J Cardiol 1995;76:12B-16B.
8. Manchanda SC, Krishnaswani S. Combination treatment with trimetazidine and diltiazem in stable angina pectoris. Heart. 1997;78:353-357.
9. Harpey C, Clauser P, Labrid C, Freyria JL, Poirier JP. Trimetazidine, a cellular anti-ischemic agent. Cardiovasc Drug Rev. 1989;6:292-312.
10. 31P NMR spectroscopy in the isolated rat heart. Arch Int Pharmacodyn Ther. 1987;286:97-110.
11. Kay L, Finelli C, Aussedat J, Guarnieri C, Rossi A. Improvement of long term preservation of the isolated arrested rat heart by trimetazidine: effects of the energy state and mitochondrial function. Am J Cardiol. 1995;76:45B-49B.
12. Opie LH. Metabolism of the heart in health and disease. Am Heart J. 1968;76:685-689.
13. Taegetmeyer H. Energy metabolism in the heart: from basic concepts to clinical application. Curr Prob Cardiol. 1994;19:59-113.
14. Lopaschuk GD, Belke DD, Gamble J, Itoi I, Schönekess BO. Regulation of fatty acid oxidation in the mammalian heart in health and disease. Biochim Biophys Acta. 1994;1213:263-276.
15. Stanley WC, Lopaschuk GD, Hall JL, McCormack JG. Regulation of myocardial carbohydrate metabolism under normal and ischemic conditions: potential for pharmacological interventions. Cardiovasc Res. 1997;33:243-257.
16. Fantini E, Demaison L, Sentex E, Grynberg A, Athias P. Some biochemical aspects of the protective effect of Trimetazidine on rat cardiomyocytes during hypoxia and reoxygenation. J Mol Cell Cardiol. 1994;26 949-958.
17. 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.
18. Lopaschuk GD, Wambolt RB, Barr RL. An imbalance between glycolysis and glucose oxidation is a possible explanation for the detrimental effects of high levels of fatty acids during aerobic reperfusion of ischemic hearts. J Pharmacol Exp Ther. 1993;264:135-144.
19. 2 during reperfusion of ischemic hearts. Am J Physiol. 1996;270:H72-H80.
20. 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.
21. Pierce GN, Czubryt MP. The contribution of ionic imbalance to ischemia/reperfusion-induced injury. J Mol Cell Cardiol. 1995;27:53-63.
22. + and pH during ischemia and reperfusion. J Mol Cell Cardiol. 1999;31:A53. Abstract.
23. Collins-Nakai RL, Noseworthy D, Lopaschuk GD. Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. Am J Physiol. 1994;267:H1862-H1871.
24. Constantin-Teodosiu D, Cederblad G, Hultman E. A sensitive radio-isotopic assay of pyruvate dehydrogenase complex in human muscle tissue. Anal Biochem. 1991;198:347-351.
25. Grimbert S, Fisch C, Deschamps D, Berson A, Fromenty B, Feldman G, Pessayre D. Effects of female sex hormones on mitochondria: possible role in acute fatty liver of pregnancy. Am J Physiol. 1995;268: G107-G115.
26. Wanders RJA, Ijlst L, Poggi F, Bonnefont JP, Munnich A, Brivet M, Rabier D, Saudubray JM. Human trifunctional protein deficiency: a new disorder of mitochondrial fatty acid β-oxidation. Biochem Biophys Res Commun. 1992;188:1139-1145.
27. Venizelos N, Ijlst L, Wanders RJA, Hagenfeldt L. β-Oxidation enzymes in fibroblasts from patients with 3-hydroxydicarboxylic aciduria. Pediatr Res. 1994;36:111-114.
28. Saddik M, Gamble J, Witters LA, Lopaschuk GD. Acetyl CoA carboxylase regulation of fatty acid oxidation in the heart. J Biol Chem. 1993;268:25836-25845.
29. Kudo N, Barr A, Barr R, Desai S, Lopaschuk GD. High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem. 1995; 270:17513-17520.
30. Hardie DG, Salt IP, Hawley SA, Davies SP. AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge. Biochem J. 1999;338:717-722.
31. Dyck JRB, Barr AJ, Barr RL, Kolattukudy PE, Lopaschuk GD. Characterization of cardiac malonyl CoA decarboxylase and its putative role in regulating fatty acid oxidation. Am J Physiol. 1998;275: H2122-H2129.
32. Randle PJ, Hales CN, Garland PB, Newsholme EA. The glucose fatty-acid cycle: its role in insulin sensitivity and the metabolic disturbances of diabetic mellitus. Lancet. 1963;i:785-789.
33. Willoughby SR, Chirkov YY, Kennedy JA, Murphy GA, Chirkova LP, Horowitz JD. Inhibition of long-chain fatty acid metabolism does not effect platelet aggregation responses. Eur J Pharmacol. 1998;356: 207-213.
34. Lopaschuk GD, Spafford MA, Davies NJ, Wall SR. Glucose and palmitate oxidation in isolated working rat hearts reperfused following a period of transient global ischemia. Circ Res. 1989;66:546-553.
35. Schulz H. Beta oxidation of fatty acids. Biochim Biophys Acta. 1991; 1081:109-120.
36. Sellier P, Audouin P, Payen B, Corona P, Duong TC, Ourbak P. Acute effects of trimetazidine evaluated by exercise testing. Eur J Clin Pharmacol. 1987;33:205-207.