ω-3 polyunsaturated fatty acid supplementation for the treatment of heart failure: Mechanisms and clinical potential

Cardiovascular Research

Volumn 84, Issue 1, 2009, Pages 33-41

  Duda, Monika K ^a   O'Shea, Karen M ^b,c   Stanley, William C ^b,c  

^a MEDICAL CENTER FOR POSTGRADUATE EDUCATION   (Poland)

^b UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^c CASE WESTERN RESERVE UNIVERSITY   (United States)

Author keywords

Linolenic acid; Cardiac; Docosahexaenoic acid; Eicosapentaenoic acid; Inflammation; Metabolism

Indexed keywords

ADIPONECTIN; ANGIOTENSIN RECEPTOR ANTAGONIST; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DOCOSAHEXAENOIC ACID; ICOSAPENTAENOIC ACID; INTERLEUKIN 1; INTERLEUKIN 6; LINOLENIC ACID; OMEGA 3 FATTY ACID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PLACEBO; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; ANTIINFLAMMATORY AGENT; CYTOKINE; ICOSANOID; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR;

CARDIOVASCULAR RISK; CLINICAL TRIAL; DIET SUPPLEMENTATION; DIETARY INTAKE; DRUG DOSE INCREASE; DRUG MEGADOSE; EPIDEMIOLOGICAL DATA; HEART FAILURE; HEART PROTECTION; HUMAN; HYPERTRIGLYCERIDEMIA; LIPOGENESIS; LOW DRUG DOSE; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROGNOSIS; RECOMMENDED DRUG DOSE; REVIEW; TRIACYLGLYCEROL BLOOD LEVEL; ANIMAL; BIOSYNTHESIS; BLOOD; DISEASE MODEL; METABOLISM; MITOCHONDRION; PHYSIOLOGY;

ADIPONECTIN; ALPHA-LINOLENIC ACID; ANIMALS; ANTI-INFLAMMATORY AGENTS; CYTOKINES; DIETARY SUPPLEMENTS; DISEASE MODELS, ANIMAL; EICOSANOIDS; FATTY ACIDS, OMEGA-3; HEART FAILURE; HUMANS; MITOCHONDRIA; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; TRIGLYCERIDES;

EID: 70350601103     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvp169     Document Type: Review

References (127)

1. Hunt SA. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2005;46:e1-e81.
2. Coats AJ. Angiotensin type-1 receptor blockers in heart failure. Prog Cardiovasc Dis 2002;44:231-242.
3. Bristow MR, Gilbert EM, Abraham WT, Adams KF, Fowler MB, Hershberger RE et al. Carvedilol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure. MOCHA Investigators. Circulation 1996;94:2807-2816.
4. Colucci WS, Packer M, Bristow MR, Gilbert EM, Cohn JN, Fowler MB et al. Carvedilol inhibits clinical progression in patients with mild symptoms of heart failure. US Carvedilol Heart Failure Study Group. Circulation 1996; 94:2800-2806.
5. Mann DL, Bristow MR. Mechanisms and models in heart failure: the bio-mechanical model and beyond. Circulation 2005;111:2837-2849.
6. Ashrafian H, Frenneaux MP, Opie LH. Metabolic mechanisms in heart failure. Circulation 2007;116:434-448.
7. Stanley WC, Hoppel CL. Mitochondrial dysfunction in heart failure: potential for therapeutic interventions? Cardiovasc Res 2000;45: 805-806.
8. Sharma N, Okere IC, Duda MK, Chess DJ, O'shea KM, Stanley WC. Potential impact of carbohydrate and fat intake on pathological left ventricular hypertrophy. Cardiovasc Res 2007;73:257-268.
9. Psota TL, Gebauer SK, Kris-Etherton P. Dietary omega-3 fatty acid intake and cardiovascular risk. Am J Cardiol 2006;98:3i-18i.
10. Das UN. Beneficial effect(s) of n-3 fatty acids in cardiovascular diseases: but, why and how? Prostaglandins Leukot Essent Fatty Acids 2000;63: 351-362.
11. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Arterioscler Thromb Vasc Biol 2003;23:e20-e30.
12. Mozaffarian D. Fish and n-3 fatty acids for the prevention of fatal coronary heart disease and sudden cardiac death. Am J Clin Nutr 2008;87: 1991S-1996S.
13. Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 2006;114:82-96.
14. GISSI-Prevezione Investigators. Dietary supplementation with n-3 poly-unsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet 1999;354:447-455.
15. Weber P, Raederstorff D. Triglyceride-lowering effect of omega-3 LC-polyunsaturated fatty acids-a review. Nutr Metab Cardiovasc Dis 2000;10:28-37.
16. Jacobson TA. Role of n-3 fatty acids in the treatment of hypertriglycer-idemia and cardiovascular disease. Am J Clin Nutr 2008;87: 1981S-1990S.
17. Mozaffarian D, Bryson CL, Lemaitre RN, Burke GL, Siscovick DS. Fish intake and risk of incident heart failure. J Am Coll Cardiol 2005;45: 2015-2021. (Pubitemid 40814125)
18. Duda MK, O'shea KM, Lei B, Barrows BR, Azimzadeh AM, McElfresh TE et al. Dietary supplementation with omega-3 PUFA increases adiponec-tin and attenuates ventricular remodeling and dysfunction with pressure overload. Cardiovasc Res 2007;76:303-310.
19. Duda MK, O'shea KM, Tintinu A, Xu W, Khairallah RJ, Barrows BR et al. Fish oil, but not flaxseed oil, decreases inflammation and prevents pressure overload-induced cardiac dysfunction. Cardiovascular Res 2009;81:319-327.
20. Gissi-HF Investigators, Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1223-1230.
21. Harris WS. n-3 fatty acids and serum lipoproteins: animal studies. Am J Clin Nutr 1997;65:1611S-1616S.
22. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr 1997;65:1645S-1654S.
23. Geleijnse JM, Giltay EJ, Grobbee DE, Donders AR, Kok FJ. Blood pressure response to fish oil supplementation: metaregression analysis of randomized trials. J Hypertens 2002;20:1493-1499.
24. Pepe S, Tsuchiya N, Lakatta EG, Hansford RG. PUFA and aging modulate cardiac mitochondrial membrane lipid composition and Ca2+ activation of PDH. Am J Physiol 1999;276:H149-H158.
25. McMillin JB, Bick RJ, Benedict CR. Influence of dietary fish oil on mito-chondrial function and response to ischemia. Am J Physiol 1992;263: H1479-H1485.
26. Roche HM. Unsaturated fatty acids. Proc Nutr Soc 1999;58:397-401.
27. Jump DB. The biochemistry of n-3 polyunsaturated fatty acids. J Biol Chem 2002;277:8755-8758.
28. Burdge GC, Jones AE, Wootton SA. Eicosapentaenoic and docosapentae-noic acids are the principal products of alpha-linolenic acid metabolism in young men. Br J Nutr 2002;88:355-363.
29. Burdge GC, Wootton SA. Conversion of alpha-linolenic acid to eicosapen-taenoic, docosapentaenoic and docosahexaenoic acids in young women. Br J Nutr 2002;88:411-420.
30. Gerster H. Can adults adequately convert alpha-linolenic acid (18:3n-3) to eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)? Int J Vitam Nutr Res 1998;68:159-173.
31. Harris WS, Miller M, Tighe AP, Davidson MH, Schaefer EJ. Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives. Atherosclerosis 2008;197:12-24.
32. Wang C, Harris WS, Chung M, Lichtenstein AH, Balk EM, Kupelnick B et al. n-3 Fatty acids from fish or fish-oil supplements, but not alpha-linolenic acid, benefit cardiovascular disease outcomes in primary-and secondary-prevention studies: a systematic review. Am J Clin Nutr 2006;84:5-17.
33. Salem NR, Pawlosky R, Wegher B, Hibbeln J. In vivo conversion of lino-leic acid to arachidonic acid in human adults. Prostaglandins Leukot Essent Fatty Acids 1999;60:407-410.
34. Simopoulos AP. Essential fatty acids in health and chronic disease. Am J Clin Nutr 1999;70:560S-569S.
35. Wijendran V, Hayes KC. Dietary n-6 and n-3 fatty acid balance and cardiovascular health. Annu Rev Nutr 2004;24:597-615.
36. Harris WS. The omega-6/omega-3 ratio and cardiovascular disease risk: uses and abuses. Curr Atheroscler Rep 2006;8:453-459.
37. Gebauer SK, Psota TL, Harris WS, Kris-Etherton PM. n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits. Am J Clin Nutr 2006;83:1526S-1535S.
38. Robinson JG. Antiatherosclerotic and antithrombotic effects of omega-3 fatty acids. Am J Cardiol 2006;98:39i-49i.
39. Harris WS, Assaad B, Poston WC. Tissue omega-6/omega-3 fatty acid ratio and risk for coronary artery disease. Am J Cardiol 2006;98:19i-26i.
40. Harris WS, Rambjor GS, Windsor SL, Diederich D. n-3 fatty acids and urinary excretion of nitric oxide metabolites in humans. Am J Clin Nutr 1997;65:459-464.
41. Jump DB, Botolin D, Wang Y, Xu J, Christian B, Demeure O. Fatty acid regulation of hepatic gene transcription. J Nutr 2005;135:2503-2506.
42. Le Jossic-Corcos C, Gonthier C, Zaghini I, Logette E, Shechter I, Bournot P. Hepatic farnesyl diphosphate synthase expression is suppressed by polyunsaturated fatty acids. Biochem J 2005;385:787-794.
43. Zaima N, Sugawara T, Goto D, Hirata T. Trans geometric isomers of EPA decrease LXRalpha-induced cellular triacylglycerol via suppression of SREBP-1c and PGC-1beta. J Lipid Res 2006;47:2712-2717.
44. Nakamura MT, Cheon Y, Li Y, Nara TY. Mechanisms of regulation of gene expression by fatty acids. Lipids 2004;39:1077-1083.
45. Pawar A, Botolin D, Mangelsdorf DJ, Jump DB. The role of liver X receptor-alpha in the fatty acid regulation of hepatic gene expression. J Biol Chem 2003;278:40736-40743.
46. Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J et al. Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology 2003;125:544-555.
47. Harris WS, Bulchandani D. Why do omega-3 fatty acids lower serum triglycerides? Curr Opin Lipidol 2006;17:387-393.
48. Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ et al. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999;3:397-403.
49. Khan S, Minihane AM, Talmud PJ, Wright JW, Murphy MC, Williams CM et al. Dietary long-chain n-3 PUFAs increase LPL gene expression in adipose tissue of subjects with an atherogenic lipoprotein phenotype. J Lipid Res 2002;43:979-985.
50. Park Y, Harris WS. Omega-3 fatty acid supplementation accelerates chy-lomicron triglyceride clearance. J Lipid Res 2003;44:455-463.
51. Harris WS, Lu G, Rambjor GS, Walen AT, Ontko JA, Cheng Q et al. Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases. Am J Clin Nutr 1997;66:254-260.
52. Sethi S, Ziouzenkova O, Ni H, Wagner DD, Plutzky J, Mayadas TN. Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alpha. Blood 2002;100:1340-1346.
53. Kliewer SA, Sundseth SS, Jones SA, Brown PJ, Wisely GB, Koble CS et al. Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors alpha and gamma. Proc Natl Acad Sci USA 1997;94:4318-4323.
54. Lei B, Lionetti V, Young ME, Chandler MP, D' Agostino C, Kang E et al. Paradoxical downregulation of the glucose oxidation pathway despite enhanced flux in severe heart failure. J Mol Cell Cardiol 2004;36: 567-576.
55. Osorio JC, Stanley WC, Linke A, Castellari M, Diep QN, Panchal AR et al. Impaired myocardial fatty acid oxidation and reduced protein expression of retinoid X receptor-alpha in pacing-induced heart failure. Circulation 2002;106:606-612.
56. Stanley WC, Recchia FA, Lopaschuk GD. Myocardial substrate metabolism in the normal and failing heart. Physiol Rev 2005;85:1093-1129.
57. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation 1996;94:2837-2842.
58. Davila-Roman VG, Vedala G, Herrero P, de las FL, Rogers JG, Kelly DP et al. Altered myocardial fatty acid and glucose metabolism in idio-pathic dilated cardiomyopathy. J Am Coll Cardiol 2002;40:271-277.
59. Pepe S, McLennan PL. Cardiac membrane fatty acid composition modulates myocardial oxygen consumption and postischemic recovery of contractile function. Circulation 2002;105:2303-2308.
60. Pepe S, McLennan PL. (n-3) Long chain PUFA dose-dependently increase oxygen utilization efficiency and inhibit arrhythmias after saturated fat feeding in rats. J Nutr 2007;137:2377-2383.
61. Castellani S, Paladini B, Paniccia R, Di Serio C, Valloti B, Ungar A et al. Increased renal formation of thromboxane A2 and prostaglandin F2 alpha in heart failure. Am Heart J 1997;133:94-100.
62. Zamorano B, Carmona MT. Prostaglandin-E2 and cyclic adenosine 30-50 monophosphate levels in the hypertrophied rat heart. Biol Res 1992; 25:85-89.
63. Newman WH, Frankis MB, Halushka PV. Increased myocardial release of prostacyclin in dogs with heart failure. J Cardiovasc Pharmacol 1983;5: 194-201.
64. Packer M. Is tumor necrosis factor an important neurohormonal mechanism in chronic heart failure? Circulation 1995;92:1379-1382.
65. Levine B, Kalman J, Mayer L, Fillit HM, Packer M. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990;323:236-241.
66. Aukrust P, Gullestad L, Ueland T, Damas JK, Yndestad A. Inflammatory and anti-inflammatory cytokines in chronic heart failure: potential therapeutic implications. Ann Med 2005;37:74-85.
67. Sharma R, Bolger AP, Li W, Davlouros PA, Volk HD, Poole-Wilson PA et al. Elevated circulating levels of inflammatory cytokines and bacterial endotoxin in adults with congenital heart disease. Am J Cardiol 2003; 92:188-193.
68. Aukrust P, Yndestad A, Ueland T, Damas JK, Gullestad L. Anti-inflammatory trials in chronic heart failure. Heart Fail Monit 2006;5: 2-9.
69. Hara A, Yuhki K, Fujino T, Yamada T, Takayama K, Kuriyama S et al. Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor. Circulation 2005;112:84-92.
70. Sun M, Chen M, Dawood F, Zurawska U, Li JY, Parker T et al. Tumor necrosis factor-alpha mediates cardiac remodeling and ventricular dysfunction after pressure overload state. Circulation 2007;115: 1398-1407.
71. Lemaitre RN, King IB, Raghunathan TE, Pearce RM, Weinmann S, Knopp RH et al. Cell membrane trans-fatty acids and the risk of primary cardiac arrest. Circulation 2002;105:697-701.
72. Luostarinen R, Boberg M, Saldeen T. Fatty acid composition in total phospholipids of human coronary arteries in sudden cardiac death. Atherosclerosis 1993;99:187-193.
73. Jenkins CM, Cedars AM, Gross RW. Eicosanoid signalling pathways in the heart. Cardiovasc Res 2009;82:240-249.
74. Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A et al. Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation 2004;110:1645-1649.
75. Gibney MJ, Hunter B. The effects of short-and long-term supplementation with fish oil on the incorporation of n-3 polyunsaturated fatty acids into cells of the immune system in healthy volunteers. Eur J Clin Nutr 1993;47:255-259.
76. Healy DA, Wallace FA, Miles EA, Calder PC, Newsholme P. Effect of low-to-moderate amounts of dietary fish oil on neutrophil lipid composition and function. Lipids 2000;35:763-768.
77. Mantzioris E, Cleland LG, Gibson RA, Neumann MA, Demasi M, James MJ. Biochemical effects of a diet containing foods enriched with n-3 fatty acids. Am J Clin Nutr 2000;72:42-48.
78. LeBlanc CJ, Horohov DW, Bauer JE, Hosgood G, Mauldin GE. Effects of dietary supplementation with fish oil on in vivo production of inflammatory mediators in clinically normal dogs. Am J Vet Res 2008;69:486-493.
79. Nordøy A, Hatcher L, Goodnight S, Fitzgerald GA, Conner WE. Effects of dietary fat content, saturated fatty acids, and fish oil on eicosanoid production and hemostatic parameters in normal men. J Lab Clin Med 1994; 123:914-920.
80. Mehta JL, Lopez LM, Lawson D, Wargovich TJ, Williams LL. Dietary supplementation with omega-3 polyunsaturated fatty acids in patients with stable coronary heart disease. Effects on indices of platelet and neutro-phil function and exercise performance. Am J Med 1988;84:45-52.
81. Simopoulos AP. Omega-3 fatty acids in inflammation and autoimmune diseases. J Am Coll Nutr 2002;21:495-505.
82. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G et al. Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflam-mation signals. J Exp Med 2002;196:1025-1037.
83. Serhan CN. Systems approach with inflammatory exudates uncovers novel anti-inflammatory and pro-resolving mediators. Prostaglandins Leukot Essent Fatty Acids 2008;79:157-163.
84. Thies F, Nebe-von-Caron G, Powell JR, Yaqoob P, Newsholme EA, Calder PC. Dietary supplementation with eicosapentaenoic acid, but not with other long-chain n-3 or n-6 polyunsaturated fatty acids, decreases natural killer cell activity in healthy subjects aged.55 y. Am J Clin Nutr 2001;73:539-548.
85. Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM, Rifai N et al. Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women. J Nutr 2004;134: 1806-1811.
86. Lennie TA, Chung ML, Habash DL, Moser DK. Dietary fat intake and proin-flammatory cytokine levels in patients with heart failure. J Card Fail 2005;11:613-618.
87. Mehra MR, Lavie CJ, Ventura HO, Milani RV. Fish oils produce anti-inflammatory effects and improve body weight in severe heart failure. J Heart Lung Transplant 2006;25:834-838.
88. Valen G, Yan ZQ, Hansson GK. Nuclear factor kappa-B and the heart. J Am Coll Cardiol 2001;38:307-314.
89. Wong SC, Fukuchi M, Melnyk P, Rodger I, Giaid A. Induction of cyclooxygenase-2 and activation of nuclear factor-kappaB in myocardium of patients with congestive heart failure. Circulation 1998;98: 100-103.
90. Matsumori A, Sasayama S. The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure. Heart Fail Rev 2001;6:129-136.
91. Zhao Y, Joshi-Barve S, Barve S, Chen LH. Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr 2004;23:71-78.
92. Takano H, Nagai T, Asakawa M, Toyozaki T, Oka T, Kumoro I et al. Peroxisome proliferator-activated receptor activators inhibit lipopolysaccharide-induced tumor necrosis factor-alpha expression in neonatal rat cardiac myocytes. Circ Res 2000;87:596-602.
93. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H et al. Adi-ponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 2000;102:1296-1301.
94. Shibata R, Ouchi N, Ito M, Kihara S, Shiojima I, Pimentel DR et al. Adiponectin-mediated modulation of hypertrophic signals in the heart. Nat Med 2004;10:1384-1389.
95. Shibata R, Sato K, Pimentel DR, Takemura Y, Kihara S, Ohashi K et al. Adiponectin protects against myocardial ischemia-reperfusion injury through. Nat Med 2005;11:1096-1103.
96. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291:1730-1737.
97. Ouchi N, Shibata R, Walsh K. Targeting adiponectin for cardioprotection. Expert Opin Ther Targets 2006;10:573-581.
98. Neschen S, Morino K, Rossbacher JC, Pongratz RL, Cline GW, Sono S et al. Fish oil regulates adiponectin secretion by a peroxisome proliferator-activated receptor-gamma-dependent mechanism in mice. Diabetes 2006;55:924-928.
99. Flachs P, Mohamed-Ali V, Horakova O, Rossmeisl M, Hosseinzadeh-Attar MJ, Hensler M et al. Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet. Diabetolo-gia 2006;49:394-397.
100. Itoh M, Suganami T, Satoh N, Tanimoto-Koyama K, Yuan X, Tanaka M et al. Increased adiponectin secretion by highly purified eicosapentae-noic acid in rodent models of obesity and human obese subjects. Arter-ioscler Thromb Vasc Biol 2007;27:1918-1925.
101. Shibata R, Ouchi N, Kihara S, Sato K, Funahashi T, Walsh K. Adiponectin stimulates angiogenesis in response to tissue ischemia through stimulation of amp-activated protein kinase signaling. J Biol Chem 2004; 279:28670-28674. (Pubitemid 38900150)
102. Engeli S, Feldpausch M, Gorzelniak K, Hartwig F, Heintze U, Janke J et al. Association between adiponectin and mediators of inflammation in obese women. Diabetes 2003;52:942-947.
103. Morgan DR, Dixon LJ, Hanratty CG, El Sherbeeny N, Hamilton PB, McGrath LTet al. Effects of dietary omega-3 fatty acid supplementation on endothelium-dependent vasodilation in patients with chronic heart failure. Am J Cardiol 2006;97:547-551.
104. Mozaffarian D, Geelen A, Brouwer IA, Geleijnse JM, Zock PL, Katan MB. Effect of fish oil on heart rate in humans: a meta-analysis of randomized controlled trials. Circulation 2005;112:1945-1952.
105. Mozaffarian D, Rimm EB. Fish intake, contaminants, and human health: evaluating the risks and the benefits. JAMA 2006;296:1885-1899.
106. Yamagishi K, Iso H, Date C, Fukui M, Wakai K, Kikuchi S et al. Fish, omega-3 polyunsaturated fatty acids, and mortality from cardiovascular diseases in a nationwide community-based cohort of Japanese men and women: The JACC (Japan Collaborative Cohort Study for Evaluation of Cancer Risk) Study. J Am Coll Cardiol 2008;52:988-996.
107. Kris-Etherton PM, Harris WS, Appel LJ. Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 2002; 106:2747-2757.
108. Kannel WB, Plehn JF, Cupples LA. Cardiac failure and sudden death in the Framingham Study. Am Heart J 1988;115:869-875.
109. McLennan PL. Myocardial membrane fatty acids and the antiarrhythmic actions of dietary fish oil in animal models. Lipids 2001;36:S111-S114.
110. McLennan PL, Bridle TM, Abeywardena MY, Charnock JS. Comparative efficacy of n-3 and n-6 polyunsaturated fatty acids in modulating ventricular fibrillation threshold in marmoset monkeys. Am J Clin Nutr 1993;58:666-669.
111. Leaf A, Kang JX, Xiao YF, Billman GE. Clinical prevention of sudden cardiac death by n-3 polyunsaturated fatty acids and mechanism of prevention of arrhythmias by n-3 fish oils. Circulation 2003;107:2646-2652.
112. Leaf A, Xiao YF, Kang JX, Billman GE. Membrane effects of the n-3 fish oil fatty acids, which prevent fatal ventricular arrhythmias. J Membr Biol 2005;206:129-139.
113. Matthan NR, Jordan H, Chung M, Lichtenstein AH, Lathrop DA, Lau J. A systematic review and meta-analysis of the impact of omega-3 fatty acids on selected arrhythmia outcomes in animal models. Metabolism 2005;54:1557-1565.
114. Leaf A, Xiao YF, Kang JX, Billman GE. Prevention of sudden cardiac death by n-3 polyunsaturated fatty acids. Pharmacol Ther 2003;98:355-377.
115. Takahashi R, Okumura K, Asai T, Hirai T, Murakami H, Murakami R et al. Dietary fish oil attenuates cardiac hypertrophy in lipotoxic cardiomyo-pathy due to systemic carnitine deficiency. Cardiovasc Res 2005;68: 213-223.
116. Bayer AL, Heidkamp MC, Patel N, Porter M, Engman S, Samarel AM. Alterations in protein kinase C isoenzyme expression and autophosphor-ylation during the progression of pressure overload-induced left ventricular hypertrophy. Mol Cell Biochem 2003;242:145-152.
117. Harris WS. Alpha-linolenic acid: a gift from the land? Circulation 2005; 111:2872-2874.
118. Campos H, Baylin A, Willett WC. Alpha-linolenic acid and risk of nonfatal acute myocardial infarction. Circulation 2008;118:339-345.
119. Djousse L, Arnett DK, Carr JJ, Eckfeldt JH, Hopkins PN, Province MA et al. Dietary linolenic acid is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the National Heart, Lung, and Blood Institute Family Heart Study. Circulation 2005;111:2921-2926.
120. Fiaccavento R, Carotenuto F, Minieri M, Masuelli L, Vecchini A, Bei R et al. Alpha-linolenic acid-enriched diet prevents myocardial damage and expands longevity in cardiomyopathic hamsters. Am J Pathol 2006;169:1913-1924.
121. De LM, Renaud S, Mamelle N, Salen P, Martin JL, Monjaud I et al. Mediterranean alpha-linolenic acid-rich diet in secondary prevention of coronary heart disease. Lancet 1994;343:1454-1459.
122. Hu FB, Stampfer MJ, Manson JE, Rimm EB, Wolk A, Colditz GA et al. Dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease among women. Am J Clin Nutr 1999;69:890-897. (Pubitemid 29205061)
123. Baylin A, Kabagambe EK, Ascherio A, Spiegelman D, Campos H. Adipose tissue alpha-linolenic acid and nonfatal acute myocardial infarction in Costa Rica. Circulation 2003;107:1586-1591. (Pubitemid 36397325)
124. Djousse L, Hunt SC, Arnett DK, Province MA, Eckfeldt JH, Ellison RC. Dietary linolenic acid is inversely associated with plasma triacylglycerol: the National Heart, Lung, and Blood Institute Family Heart Study. Am J Clin Nutr 2003;78:1098-1102.
125. Guivernau M, Meza N, Barja P, Roman O. Clinical and experimental study on the long-term effect of dietary gamma-linolenic acid on plasma lipids, platelet aggregation, thromboxane formation, and prostacyclin production. Prostaglandins Leukot Essent Fatty Acids 1994;51:311-316.
126. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ. The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 1996;63:116-122.
127. James MJ, Gibson RA, Cleland LG. Dietary polyunsaturated fatty acids and inflammatory mediator production. Am J Clin Nutr 2000;71: 343S-348S.