Metabolic abnormalities of the heart in type II diabetes

Diabetes and Vascular Disease Research

Volumn 12, Issue 4, 2015, Pages 239-248

  Amaral, Nelson ^a   Okonko, Darlington O ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

diabetes; energetics; Metabolism

Indexed keywords

ACETYL COENZYME A; ACIPIMOX; ADENOSINE TRIPHOSPHATASE (CALCIUM); ADVANCED GLYCATION END PRODUCT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; CARNITINE PALMITOYLTRANSFERASE I; ETOMOXIR; EXENDIN 4; FATTY ACID; FLAVINE ADENINE NUCLEOTIDE; GLICLAZIDE; GLUCOSE TRANSPORTER; LIRAGLUTIDE; METFORMIN; PERHEXILINE; PYRUVATE DEHYDROGENASE KINASE; RANOLAZINE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RESVERATROL; ROSIGLITAZONE; RYANODINE RECEPTOR; SARCOPLASMIC RETICULUM CALCIUM TRANSPORTING ADENOSINE TRIPHOSPHATASE; SAXAGLIPTIN; TRIMETAZIDINE; UBIDECARENONE; UBIQUINOL CYTOCHROME C REDUCTASE; 10-(6'-UBIQUINONYL)DECYLTRIPHENYLPHOSPHONIUM BROMIDE; ANTIOXIDANT; CARDIOVASCULAR AGENT; GLUCOSE; ORGANOPHOSPHORUS COMPOUND; UBIQUINONE;

ANGINA PECTORIS; ANTIOXIDANT ACTIVITY; CARDIOVASCULAR RISK; CITRIC ACID CYCLE; CLINICAL TRIAL (TOPIC); DIABETIC CARDIOMYOPATHY; DIASTOLIC DYSFUNCTION; DRUG BINDING SITE; ELECTRON TRANSPORT; ENERGY TRANSFER; FATTY ACID METABOLISM; FATTY ACID TRANSPORT; GLUCOSE TRANSPORT; HEART FAILURE; HEART INFARCTION; HEART LEFT VENTRICLE FAILURE; HEART MUSCLE METABOLISM; HUMAN; HYPERTROPHIC CARDIOMYOPATHY; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE PHOSPHORYLATION; REVIEW; ANALOGS AND DERIVATIVES; COMPLICATION; DIABETIC CARDIOMYOPATHIES; ENERGY METABOLISM; HEART MITOCHONDRION; HEART MUSCLE; METABOLISM; OXIDATIVE STRESS;

ANTIOXIDANTS; CARDIOVASCULAR AGENTS; DIABETES MELLITUS, TYPE 2; DIABETIC CARDIOMYOPATHIES; ENERGY METABOLISM; FATTY ACIDS; GLUCOSE; HUMANS; MITOCHONDRIA, HEART; MYOCARDIUM; ORGANOPHOSPHORUS COMPOUNDS; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PERHEXILINE; RANOLAZINE; TRIMETAZIDINE; UBIQUINONE;

EID: 84936999660     PISSN: 14791641     EISSN: 17528984     Source Type: Journal    
DOI: 10.1177/1479164115580936     Document Type: Review

References (111)

1. Kannel WB, McGee DL,. Diabetes and cardiovascular disease. The Framingham study. JAMA 1979; 241: 2035-2038.
2. Cubbon RM, Adams B, Rajwani A,. Diabetes mellitus is associated with adverse prognosis in chronic heart failure of ischaemic and non-ischaemic aetiology. Diab Vasc Dis Res 2013; 10: 330-336.
3. MacDonald MR, Petrie MC, Varyani F,. Impact of diabetes on outcomes in patients with low and preserved ejection fraction heart failure: an analysis of the Candesartan in heart failure: assessment of reduction in mortality and morbidity (CHARM) programme. Eur Heart J 2008; 29: 1377-1385.
4. Buse JB, Ginsberg HN, Bakris GL,.; American Heart Association; American Diabetes Association. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007; 30: 162-172.
5. Rubler S, Dlugash J, Yuceoglu YZ,. New type of cardiomyopathy associated with diabetic glomerulosclerosis. Am J Cardiol 1972; 30: 595-602.
6. Devereux RB, Roman MJ, Paranicas M,. Impact of diabetes on cardiac structure and function: the strong heart study. Circulation 2000; 101: 2271-2276.
7. Miki T, Yuda S, Kouzu H,. Diabetic cardiomyopathy: pathophysiology and clinical features. Heart Fail Rev 2013; 18: 149-166.
8. Di Bonito P, Moio N, Cavuto L,. Early detection of diabetic cardiomyopathy: usefulness of tissue Doppler imaging. Diabet Med 2005; 22: 1720-1725.
9. Schannwell CM, Schneppenheim M, Perings S,. Left ventricular diastolic dysfunction as an early manifestation of diabetic cardiomyopathy. Cardiology 2002; 98: 33-39.
10. Andersen NH, Poulsen SH, Eiskjaer H,. Decreased left ventricular longitudinal contraction in normotensive and normoalbuminuric patients with Type II diabetes mellitus: a Doppler tissue tracking and strain rate echocardiography study. Clin Sci 2003; 105: 59-66.
11. Ernande L, Rietzschel ER, Bergerot C,. Impaired myocardial radial function in asymptomatic patients with type 2 diabetes mellitus: a speckle tracking imaging study. J Am Soc Echocardiogr 2010; 23: 1266-1272.
12. Ward ML, Crossman DJ,. Mechanisms underlying the impaired contractility of diabetic cardiomyopathy. World J Cardiol 2014; 6: 577-584.
13. Pereira L, Ruiz-Hurtado G, Rueda A,. Calcium signaling in diabetic cardiomyocytes. Cell Calcium. Epub ahead of print 17 2014. DOI: 10.1016/j.ceca.2014.08.004.
14. Boudina S, Sena S, Theobald H,. Mitochondrial energetics in the heart in obesity related diabetes: direct evidence for increased uncoupled respiration and activation of uncoupling proteins. Diabetes 2007; 56: 2457-2466.
15. Belke DD, Larsen TS, Gibbs EM,. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab 2000; 279: e1104-e1113.
16. Scheuermann-Freestone M, Madsen PL, Manners D,. Abnormal cardiac and skeletal muscle energy metabolism in patients with type 2 diabetes. Circulation 2003; 107: 3040-3046.
17. Zhou YT, Grayburn P, Karim A,. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA 2000; 97: 1784-1789.
18. Ashrafian H, Neubauer S,. Metabolomic profiling of cardiac substrate utilization: fanning the flames of systems biology? Circulation 2009; 119: 1700-1702.
19. Weiss RG, Maslov M,. Normal myocardial metabolism: fueling cardiac contraction. Adv Stud Med 2004; 4: S457-S463.
20. Neubauer S,. The failing heart-an engine out of fuel. N Engl J Med 2007; 356: 1140-1151.
21. Taegtmeyer H, Golfman L, Sharma S,. Linking gene expression to function: metabolic flexibility in the normal and diseased heart. Ann NY Acad Sci 2004; 1015: 202-213.
22. Neely JR, Rovetto MJ, Oram JF,. Myocardial utilization of carbohydrate and lipids. Prog Cardiovasc Dis 1972; 15: 289-329.
23. Wisnecki JA, Gertz EW, Neese RA,. Myocardial metabolism of free fatty acids: studies with 14C labelled substrates in humans. J Clin Invest 1987; 79: 359-366.
24. Lopaschuk GD, Ussher JR, Folmes CD,. Myocardial fatty acid metabolism in health and disease. Physiol Rev 2010; 90: 207-258.
25. Saddik M, Lopaschuk GD,. Myocardial triglyceride turnover and contribution to energy substrate utilization in isolated working rat hearts. J Biol Chem 1991; 266: 8162-8170.
26. Ferre P,. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 2004; 53: S43-S50.
27. Randle PJ, Garland PB, Hales CN,. The glucose fatty-acid cycle, its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; 281: 785-789.
28. Fillmore N, Lopaschuk G,. Impact of free fatty acids on cardiac efficiency. Heart Metab 2011; 53: 33-37.
29. Depre C, Vanoverschelde JL, Taegtmeyer H,. Glucose for the heart. Circulation 1999; 99: 578-588.
30. Cotter MA, Cameron NE, Robertson S,. Polyol pathway mediated changes in cardiac muscle contractile properties: studies in streptozotocin-diabetic and galactose-fed rats. Exp Physiol 1992; 77: 829-838.
31. Wamelink MM, Struys EA, Jakobs C,. The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis 2008; 31: 703-717.
32. Schleicher ED, Weigert C,. Role of the hexosamine biosynthetic pathway in diabetic nephropathy. Kidney Int 2000; 77: S13-S18.
33. Hansford RG, Cohen L,. Relative importance of pyruvate dehydrogenase interconversion and feed-back inhibition in the effect of fatty acids on pyruvate oxidation by rat heart mitochondria. Arch Biochem Biophys 1978; 191: 65-81.
34. McCormack JG, Halestrap AP, Denton RM,. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 1990; 70: 391-425.
35. Papa S, Martino PL, Capitanio G,. The oxidative phosphorylation system in mammalian mitochondria. Adv Exp Med Biol 2012; 942: 3-37.
36. Des Rosiers C, Labarthe F, Lloyd SG,. Cardiac anaplerosis in health and disease: food for thought. Cardiovasc Res 2011; 90: 210-219.
37. Murphy JP,. How mitochondria produce reactive oxygen species. Biochem J 2009; 417: 1-13.
38. Beard JL,. Iron biology in immune function, muscle metabolism, and neuronal functioning. J Nutr 2001; 131: 568-580.
39. Crack JC, Green J, Thomson AJ,. Iron-sulfur cluster sensor-regulators. Curr Opin Chem Biol 2012; 16: 35-44.
40. Park SY, Gifford JR, Andtbacka RH,. Cardiac, skeletal, and smooth muscle respiration: are all mitochondria created equal? Am J Physiol Heart Circ Physiol 2014; 307: 346-352.
41. Lemieux H, Hoppel CL,. Mitochondria in the human heart. J Bioenerg Biomembr 2009; 41: 99-106.
42. Zick M, Rabl R, Reichert AS,. Cristae formation-linking ultrastructure and function of mitochondria. Biochim Biophys Acta 2009; 1793: 5-19.
43. Labbe SM, Grenier-Larouche T, Noll C,. Increased myocardial uptake of dietary fatty acids linked to cardiac dysfunction in glucose-intolerant humans. Diabetes 2012; 61: 2701-2710.
44. Cha DR, Han JY, Su DM,. Peroxisome proliferator-activated receptor-alpha deficiency protects aged mice from insulin resistance induced by high-fat diet. Am J Nephrol 2007; 27: 479-482.
45. Rijzewijk LJ, Van der Meer RW, Lamb HJ,. Altered myocardial substrate metabolism and decreased diastolic function in nonischemic human diabetic cardiomyopathy: studies with cardiac positron emission tomography and magnetic resonance imaging. J Am Coll Cardiol 2009; 54: 1524-1532.
46. McGavock JM, Lingvay I, Zib I,. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007; 116: 1170-1175.
47. Rijzewijk LJ, Van der Meer RW, Smit JW,. Myocardial steatosis is an independent predictor of diastolic dysfunction in type 2 diabetes mellitus. J Am Coll Cardiol 2008; 52: 1793-1799.
48. Ng AC, Delgado V, Bertini M,. Myocardial steatosis and biventricular strain and strain rate imaging in patients with type 2 diabetes mellitus. Circulation 2010; 122: 2538-2544.
49. Du Z, Edelstein D, Obici S,. Insulin resistance reduces arterial prostacyclin synthase and eNOS activities by increasing endothelial fatty acid oxidation. J Clin Invest 2006; 116: 1071-1080.
50. Hafstad AD, Nabeebaccus AA, Shah AM,. Novel aspects of ROS signalling in heart failure. Basic Res Cardiol 2013; 108: 359.
51. Perry DK, Hannun YA,. The role of ceramide in cell signaling. Biochim Biophys Acta 1998; 1436: 233-243.
52. Drosatos K, Schulze PC,. Cardiac lipotoxicity: molecular pathways and therapeutic implications. Curr Heart Fail Rep 2013; 10: 109-121.
53. How OJ, Aasum E, Severson DL,. Increased myocardial oxygen consumption reduces cardiac efficiency in diabetic mice. Diabetes 2006; 55: 466-473.
54. Hafstad AD, Solevåg GH, Severson DL,. Perfused hearts from type 2 diabetic (db/db) mice show metabolic responsiveness to insulin. Am J Physiol Heart Circ Physiol 2006; 290: 1763-1769.
55. Armoni M, Harel C, Bar-Yoseph F,. Free fatty acids repress the GLUT4 gene expression in cardiac muscle via novel response elements. J Biol Chem 2005; 280: 34786-34795.
56. Utriainen T, Takala T, Luotolahti M,. Insulin resistance characterizes glucose uptake in skeletal muscle but not in the heart in NIDDM. Diabetologia 1998; 41: 555-559.
57. Schummer CM, Werner U, Tennagels N,. Dysregulated pyruvate dehydrogenase complex in Zucker diabetic fatty rats. Am J Physiol Endocrinol Metab 2008; 294: 88-96.
58. Bowker-Kinley MM, Davis WI,. Evidence for existence of tissue-specific regulation of the mammalian pyruvate dehydrogenase complex. Biochem J 1998; 329: 191-196.
59. Holness MJ, Sugden MC,. Regulation of pyruvate dehydrogenase complex activity by reversible phosphorylation. Biochem Soc Trans 2003; 31: 1143-1151.
60. Thompson AL, Cooney GJ,. Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes 2000; 49: 1761-1765.
61. Chung SS, Ho EC, Lam KS,. Contribution of polyol pathway to diabetes-induced oxidative stress. J Am Soc Nephrol 2003; 14: 233-236.
62. Sochor M, Gonzalez AM, McLean P,. Regulation of alternative pathways of glucose metabolism in rat heart in alloxan diabetes: changes in the pentose phosphate pathway. Biochem Biophys Res Commun 1984; 118: 110-116.
63. McNulty PH,. Hexosamine biosynthetic pathway flux and cardiomyopathy in type 2 diabetes mellitus. Focus on 'Impact of type 2 diabetes and aging on cardiomyocyte function and O-linked N-acetylglucosamine levels in the heart'. Am J Physiol Cell Physiol 2007; 292: 1243-1244.
64. Laughlin MR, Petit WA Jr, Shulman RG,. Measurement of myocardial glycogen synthesis in diabetic and fasted rats. Am J Physiol 1990; 258: 184-190.
65. Petrova R, Yamamoto Y, Muraki K,. Advanced glycation endproduct-induced calcium handling impairment in mouse cardiac myocytes. J Mol Cell Cardiol 2002; 34: 1425-1431.
66. Brownlee M,. Advanced protein glycosylation in diabetes and aging. Annu Rev Med 1995; 46: 223-234.
67. Arai M,. Advanced glycation endproducts and their receptor: do they play a role in diabetic cardiomyopathy? J Mol Cell Cardiol 2002; 34: 1305-1308.
68. Roche E, Farfari S, Witters LA,. Long-term exposure of beta-INS cells to high glucose concentrations increases anaplerosis, lipogenesis, and lipogenic gene expression. Diabetes 1998; 47: 1086-1094.
69. Anderson EJ, Kypson AP, Rodriguez E,. Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol 2009; 54: 1891-1898.
70. Croston TL, Thapa D, Holden AA,. Functional deficiencies of subsarcolemmal mitochondria in the type 2 diabetic human heart. Am J Physiol Heart Circ Physiol 2014; 307: 54-65.
71. Montaigne D, Marechal X, Coisne A,. Myocardial contractile dysfunction is associated with impaired mitochondrial function and dynamics in type 2 diabetic but not in obese patients. Circulation 2014; 130: 554-564.
72. Andreyev AY, Kushnareva YE, Starkov AA,. Mitochondrial metabolism of reactive oxygen species. Biochem Mosc 2005; 70: 200-214.
73. Nishikawa T, Edelstein D, Du XL,. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 2000; 404: 787-790.
74. Giardino I, Edelstein D, Brownlee M,. BCL-2 expression or antioxidants prevent hyperglycemia induced formation of intracellular advanced glycation endproducts in bovine endothelial cells. J Clin Invest 1996; 97: 1422-1428.
75. Zorzano A, Liesa M, Palacín M,. Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes. Int J Biochem Cell Biol 2009; 41: 1846-1854.
76. Yu T, Sheu SS, Robotham JL,. Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 2008; 79: 341-351.
77. Williamson CL, Dabkowski ER, Baseler WA,. Enhanced apoptotic propensity in diabetic cardiac mitochondria: influence of subcellular spatial location. Am J Physiol Heart Circ Physiol 2010; 298: 633-642.
78. Savabi F,. Mitochondrial creatine phosphokinase deficiency in diabetic rat heart. Biochem Biophys Res Commun 1988; 154: 469-475.
79. Savabi F, Kirsch A,. Alteration of the phosphocreatine energy shuttle components in diabetic rat heart. J Mol Cell Cardiol 1991; 23: 1323-1333.
80. Diamant M, Lamb HJ, Groeneveld Y,. Diastolic dysfunction is associated with altered myocardial metabolism in asymptomatic normotensive patients with well-controlled type 2 diabetes mellitus. J Am Coll Cardiol 2003; 42: 328-335.
81. Hafstad AD, Khalid AM, How OJ,. 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 2007; 292: 1288-1294.
82. Monji A, Mitsui T, Bando YK,. Glucagon-like peptide-1 receptor activation reverses cardiac remodeling via normalizing cardiac steatosis and oxidative stress in type 2 diabetes. Am J Physiol Heart Circ Physiol 2013; 305: 295-304.
83. Liu J, Liu Y, Chen L,. Glucagon-like peptide-1 analog liraglutide protects against diabetic cardiomyopathy by the inhibition of the endoplasmic reticulum stress pathway. J Diabetes Res 2013; 2013: 630537.
84. Younce CW, Burmeister MA, Ayala JE,. Exendin-4 attenuates high glucose-induced cardiomyocyte apoptosis via inhibition of endoplasmic reticulum stress and activation of SERCA2a. Am J Physiol Cell Physiol 2013; 304: 508-518.
85. Rosiak M, Postula M, Kaplon-Cieslicka A,. Metformin treatment may be associated with decreased levels of NT-proBNP in patients with type 2 diabetes. Adv Med Sci 2013; 58: 362-368.
86. Malmberg K, Ryden L, Hamsten A,. Effects of insulin treatment on cause-specific one-year mortality and morbidity in diabetic patients with acute myocardial infarction. DIGAMI Study Group. Diabetes Insulin-Glucose in Acute Myocardial Infarction. Eur Heart J 1996; 17: 1337-1344.
87. Malmberg K, Ryden L, Wedel H,. 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.
88. Selker HP, Beshansky JR, Sheehan PR,. Out-of-hospital administration of intravenous glucose-insulin-potassium in patients with suspected acute coronary syndromes: the IMMEDIATE randomized controlled trial. JAMA 2012; 307: 1925-1933.
89. Home PD, Pocock SJ, Beck-Nielsen H,.; RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised open-label trial. Lancet 2009; 373: 2125-2135.
90. Scirica BM, Bhatt DL, Braunwald E,. SAVOR-TIMI 53 Steering Committee and Investigators Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013; 369: 1317-1326.
91. Nagendran J, Oudit GY, Bakal JA,. Are users of sulphonylureas at the time of an acute coronary syndrome at risk of poorer outcomes? Diabetes Obes Metab 2013; 15: 1022-1028.
92. Panchal AR, Stanley WC, Kerner J,. Beta-receptor blockade decreases carnitine palmitoyl transferase I activity in dogs with heart failure. J Card Fail 1998; 4: 121-126.
93. Huang H, Shan J, Pan XH,. Carvedilol protects early diabetic rat hearts through reducing oxidative stress. Conf Proc IEEE Eng Med Biol Soc 2005; 1: 929-932.
94. +)-pump ATPase of the diabetic rat heart by lipid-lowering interventions. Mol Cell Biochem 1994; 132: 69-80.
95. Belardinelli R, Cianci G, Gigli M,. Effects of trimetazidine on myocardial perfusion and left ventricular systolic function in type 2 diabetic patients with ischemic cardiomyopathy. J Cardiovasc Pharmacol 2008; 51: 611-615.
96. Kosiborod M, Arnold SV, Spertus JA,. Evaluation of ranolazine in patients with type 2 diabetes mellitus and chronic stable angina: results from the TERISA randomized clinical trial (Type 2 Diabetes Evaluation of Ranolazine in Subjects with Chronic Stable Angina). J Am Coll Cardiol 2013; 61: 2038-2045.
97. Mourouzis I, Mantzouratou P, Galanopoulos G,. The beneficial effects of ranolazine on cardiac function after myocardial infarction are greater in diabetic than in nondiabetic rats. J Cardiovasc Pharmacol Ther 2014; 19: 457-469.
98. Lee L, Campbell R, Scheuermann-Freestone 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.
99. McKenna W, Phan TT, Nallur-Shivu G,. Metabolic modulator perhexiline corrects energy deficiency and improves exercise capacity in symptomatic hypertrophic cardiomyopathy. Circulation 2010; 122: 1562-1569.
100. Drury NE, Howell NJ, Calvert MJ,. The effect of perhexiline on myocardial protection during coronary artery surgery: a two-centre, randomized, double-blind, placebo-controlled trial. Eur J Cardiothorac Surg. 2015; 47: 464-472.
101. Bersin RM, Wolfe C, Kwasman M,. Improved haemodynamic function and mechanical efficiency in congestive heart failure with sodium dichloroacetate. J Am Coll Cardiol 1994; 23: 1617-1624.
102. Lim S, Rashid MA, Jang M,. Mitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity. Cell Physiol Biochem 2011; 28: 873-886.
103. Dai DF, Chen T, Szeto H,. Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy. J Am Coll Cardiol 2011; 58: 73-82.
104. Beaudoin MS, Perry CG, Arkell AM,. Impairments in mitochondrial palmitoyl-CoA respiratory kinetics that precede development of diabetic cardiomyopathy are prevented by resveratrol in ZDF rats. J Physiol 2014; 592: 2519-2533.
105. Mortensen SA, Rosenfeldt F, Kumar A,. The effect of coenzyme Q10 on morbidity and mortality in chronic heart failure: results from Q-SYMBIO: a randomized double-blind trial. JACC Heart Fail. Epub ahead of print 1 2014. DOI: 10.1016/j.jchf.2014.06.008.
106. Huynh K, Kiriazis H, Du XJ,. Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes. Diabetologia 2012; 55: 1544-1553.
107. Okonko DO, Mandal AK, Missouris CG,. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity and survival. J Am Coll Cardiol 2011; 58: 1241-1251.
108. Naito Y, Tsujino T, Matsumoto M,. Adaptive response of the heart to long-term anemia induced by iron deficiency. Am J Physiol Heart Circ Physiol 2009; 296: 585-593.
109. Okonko DO, Grzeslo A, Witkowski T,. Effect of intravenous iron sucrose on exercise tolerance in anemic and non-anemic patients with symptomatic chronic heart failure and iron deficiency (FERRIC-HF): a randomized, controlled, observer-blinded trial. J Am Coll Cardiol 2008; 51: 103-112.
110. Anker SD, Comin Colet J, Filippatos G,. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009; 361: 1-13.
111. Maeder MT, Khammy O, dos Remedios C,. Myocardial and systemic iron depletion in heart failure implications for anemia accompanying heart failure. J Am Coll Cardiol 2011; 58: 474-480.