Eicosapentaenoic acid (EPA) reduces cardiovascular events: Relationship with the EPA/Arachidonic acid ratio

Journal of Atherosclerosis and Thrombosis

Volumn 20, Issue 12, 2013, Pages 861-877

  Ohnishi, Haruo ^a   Saito, Yasushi ^b  

^a MOCHIDA PHARMACEUTICAL CO   (Japan)

^b CHIBA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Cardiovascular disease; EPA; EPA AA ratio; PGI TXA balance; PGI3

Indexed keywords

ARACHIDONIC ACID; CHOLESTEROL; FIBROBLAST GROWTH FACTOR; FISH OIL; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; ICOSAPENTAENOIC ACID; ICOSAPENTAENOIC ACID ETHYL ESTER; INTERCELLULAR ADHESION MOLECULE 1; LOW DENSITY LIPOPROTEIN CHOLESTEROL; OMEGA 3 ACID ETHYL ESTER; OMEGA 3 FATTY ACID; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLETHANOLAMINE; PHOSPHATIDYLSERINE; PHOSPHOLIPID; PROSTAGLANDIN; PROSTAGLANDIN E2; PROSTAGLANDIN E3; SCATTER FACTOR; STATIN (PROTEIN); THROMBOXANE; TRIACYLGLYCEROL; VASCULAR CELL ADHESION MOLECULE 1; VASCULOTROPIN;

ANGIOGENESIS; BIOLOGICAL ACTIVITY; CARDIOVASCULAR DISEASE; CAROTID ENDARTERECTOMY; CELL DEATH; CLINICAL TRIAL (TOPIC); DRUG EFFICACY; HEART FAILURE; HEART MUSCLE ISCHEMIA; HUMAN; HYPERCHOLESTEROLEMIA; ISCHEMIC HEART DISEASE; NONHUMAN; PERCUTANEOUS CORONARY INTERVENTION; REVIEW; RISK FACTOR; THROMBOCYTE AGGREGATION; VASOCONSTRICTION;

ARACHIDONIC ACID; CARDIOVASCULAR DISEASES; EICOSAPENTAENOIC ACID; HUMANS;

EID: 84890819000     PISSN: 13403478     EISSN: 18803873     Source Type: Journal    
DOI: 10.5551/jat.18002     Document Type: Review

References (101)

1. Gorjão R, Azevedo-Martins AK, Rodrigues HG, Abdul-kader F, Arcisio-Miranda M, Procopio J, Curi R: Comparative effects of DHA and EPA on cell function. Pharmacol Ther, 2009; 122: 56-64
2. Arterburn LM, Hall EB, Oken H: Distribution, inter-conversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr, 2006; 83: 1467S-1476S
3. Hooper L, Thompson RL, Harrison RA, Summerbell CD, Ness AR, Moore HJ, Worthington HV, Durrington PN, Higgins J P, Capps NE, Riemersma RA, Ebrahim SB, Davey Smith G: Risks and benefits of omega 3 fats for mortality, cardiovascular disease, and cancer: systematic review. BMJ, 2006; 332: 752-760
4. Tolonen MJ: BMJ. 2006 Apr 1; 332 (7544): 752-60. 2 April 2006. http://www.bmj.com/content/332/7544/752?page=1&tab=responses
5. Ahrens EH Jr, Insull W Jr, Hirsch J, Stoffel W, Peterson ML, Farquhar JW, Iller T, Thomasson HJ: The effect on human serum-lipids of a dietary fat, highly unsaturated, but poor in essential fatty acids. Lancet, 1959; 1: 115-119
6. Kinsell LW, Michaels GD, Walker G, Visintine RE: The effect of a fish-oil fraction on plasma lipids. Diabetes, 1961; 10: 316-319
7. Hegsted DM, Jack CW, Stare FJ: The composition of human adipose tissue from several parts of the world. Am J Clin Nutr, 1962; 10: 11-18
8. Nelson AM: Diet therapy in coronary disease: effect on mortality of high-protein, high-seafood, fat-controlled diet. Geriatrics, 1972; 27: 103-116
9. Bang HO, Dyerberg J, Nielsen AB: Plasma lipid and lipoprotein pattern in Greenlandic West-coast Eskimos. Lancet, 1971; 1: 1143-1145
10. Dyerberg J, Bang HO, Hjorne N: Fatty acid composition of the plasma lipids in Greenland Eskimos. Am J Clin Nutr, 1975; 28: 958-966
11. Bang HO, Dyerberg J, Hjøorne N: The composition of food consumed by Greenland Eskimos. Acta Med Scand, 1976; 200: 69-73
12. Dyerberg J, Bang HO, Stoffersen E, Moncada S, Vane JR: Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis? Lancet, 1978; 2: 117-119
13. Fischer S, Weber PC, Dyerberg J: The prostacyclin/ thromboxane balance is favourably shifted in Greenland Eskimos. Prostaglandins, 1986; 32: 235-241
14. Kromann N, Green A: Epidemiological studies in the Upernavik district, Greenland. incidence of some chronic diseases 1950-1974. Acta Med Scand, 1980; 208: 401-406
15. Hirai A, Hamazaki T, Terano T, Nishikawa T, Tamura Y, Kumagai A, Jajiki J: Eicosapentaenoic acid and platelet function in Japanese. Lancet, 1980; 2: 1132-1133
16. Hirai A: An epidemiological study on the dietary inges-tion of eicosapentaenoic acid (EPA) and platelet function in Japanese. Nihon Naika Gakkai Zasshi, 1985; 74: 13-20
17. Dolecek TA: Epidemiological evidence of relationships between dietary polyunsaturated fatty acidsand mortality in the multiple risk factor intervention trial. Proc Soc Exp Biol Med, 1992; 200: 177-182
18. Iso H, Rexrode KM, Stampfer MJ, Manson JE, Colditz GA, Speizer FE, Hennekens CH, Willett WC: Intake of fish and omega-3 fatty acids and risk of stroke in women. JAMA, 2001; 285: 304-312
19. Gissi-HF Investigators, Tavazzi L, Maggioni A P, Marchi-oli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nico-losi GL, Porcu M, Tognoni G: Effect of n-3 polyunsatu-rated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet, 2008; 372: 1223-1230
20. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Ita-kura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shi-mada K, Shirato K: Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded end-point analysis. Lancet, 2007; 369: 1090-1098
21. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y: JELIS Investigators. Relationships between plasma fatty acid composition and coronary artery disease. J Atheroscler Thromb, 2011; 18: 99-107
22. Mozaffarian D, Lemaitre RN, King IB, Song X, Spiegel-man D, Sacks FM, Rimm EB, Siscovick DS: Circulating long-chain ω-3 fatty acids and incidence of congestive heart failure in older adults: the cardiovascular health study, Ann Intern Med, 2011 155: 160-170
23. Lee SH, Shin MJ, Kim JS, Ko YG, Kang SM, Choi D, Jang Y, Chung N, Shim WH, Cho SY, Manabe I, Ha JW: Blood eicosapentaenoic acid and docosahexaenoic acid as predictors of all-cause mortality in patients with acute myocardial infarction--data from Infarction Prognosis Study (IPS) Registry. Circ J, 2009; 73: 2250-2257
24. Domei T, Yokoi H, Kuramitsu S, Soga Y, Arita T, Ando K, Shirai S, Kondo K, Sakai K, Goya M, Iwabuchi M, Ueeda M, Nobuyoshi M: Ratio of serum n-3 to n-6 polyunsaturated fatty acids and the incidence of major adverse cardiac events in patients undergoing percutaneous coronary intervention. Circ J, 2012; 76: 423-429
25. Yamagishi K, Nettleton JA, Folsom AR: ARIC Study Investigators. Plasma fatty acid composition and incident heart failure in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study, Am Heart J, 2008; 156: 965-974
26. Broekman MJ, Ward JW, Marcus AJ: Phospholipid metabolism in stimulated human platelets. Changes in phosphatidylinositol, phosphatidic acid, and lysophos-pholipids. J Clin Invest, 1980; 66: 275-283
27. Fischer S, von Schacky C, Siess W, Strasser T, Weber PC: Uptake, release and metabolism of docosahexaenoic acid (DHA, c22: 6 omega 3) in human platelets and neutro-phils. Biochem Biophys Res Commun, 1984; 120: 907-918
28. Mahadevappa VG, Holub BJ: Quantitative loss of individual eicosapentaenoyl-relative to arachidonoyl-con-taining phospholipids in thrombin-stimulated human platelets. J Lipid Res, 1987; 28: 1275-1280
29. Weaver BJ, Holub BJ: The relative degradation of [14C] eicosapentaenoyl and [3H]arachidonoyl species of phos-phatidylinositol and phosphatidylcholine in thrombin-stimulated human platelets. Biochem Cell Biol, 1986; 64: 1256-1261
30. Kazachkov M, Chen Q, Wang L. Zou J. Substrate preferences of a lysophosphatidylcholine acyltransferase highlight its role in phospholipid remodeling. Lipids. 2008; 43: 895-902
31. Iritani N, Ikeda Y, Kajitani H: Selectivities of 1-acylglyc-erophosphorylcholine acyltransferase and acyl-CoA syn-thetase for n-3 polyunsaturated fatty acids in platelets and liver mirosomes. Biochim Biophys Acta, 1984; 793: 416-422
32. Takamura H, Kasai H, Arita H, Kito M: Phospholipid molecular species in human umbilical artery and vein endothelial cells. J Lipid Res, 1990; 31: 709-717
33. Murphy EJ, Joseph L, Stephens R, Horrocks LA: Phos-pholipid composition of cultured human endothelial cells. Lipids, 1992; 27: 150-153
34. Jamin S P, Crabos M, Catheline M, Martin-Chouly C, Legrand AB, Saïag B: Eicosapentaenoic acid reduces thrombin-evoked release of endothelin-1 in cultured bovine endothelial cells. Res Commun Mol Pathol Pharmacol, 1999; 105: 271-281
35. Martin TW, Michaelis KC: Ca2(+)-dependent synthesis of prostaglandin I2 and mobilization of arachidonic acid from phospholipids in cultured endothelial cells permea-bilized with saponin. Biochim Biophys Acta, 1990; 1054: 159-168
36. Arterburn LM, Hall EB, Oken H: Distribution, inter-conversion, and dose response of n-3 fatty acids in humans. Am J Clin Nutr, 2006; 83: 1467S-1476S
37. Hansen JB, Grimsgaard S, Nilsen H, Nordoy A, Bonaa KH: Effects of highly purified eicosapentaenoic acid and docosahexaenoic acid on fatty acid absorption, incorporation into serum phospholipids and postprandial tri-glyceridemia. Lipids, 1998; 33: 131-138
38. Mori TA, Burke V, Puddey IB, Watts GF, O'Neal DN, Best JD, Beilin LJ: Purified eicosapentaenoic and doco-sahexaenoic acids have differential effects on serum lip-ids and lipoproteins, LDL particle size, glucose, and insulin in mildly hyperlipidemic men. Am J Clin Nutr, 2000; 71: 1085-1094
39. Itakura H, Yokoyama M, Matsuzaki M, Saito Y, Origasa H, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K, Matsuzawa Y: Relationships between plasma fatty acid composition and coronary artery disease. J Athero-scler Thromb, 2011; 18: 99-107
40. Conquer JA, Holub BJ: Supplementation with an algae source of docosahexaenoic acid increases (n-3) fatty acid status and alters selected risk factors for heart disease in vegetarian subjects. J Nutr, 1996; 126: 3032-3039
41. Brossard N, Croset M, Pachiaudi C, Riou J P, Tayot JL, Lagarde M: Retroconversion and metabolism of [13C]22: 6n-3 in humans and rats after intake of a single dose of [13C]22: 6n-3-triacylglycerols. Am J Clin Nutr, 1996; 64: 577-586
42. Gerster H: Can adults adequately convert alpha-linole-nic 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
43. Crawford MA, Bloom M, Broadhurst CL, Schmidt WF, Cunnane SC, Galli C, Gehbremeskel K, Linseisen F, Lloyd-Smith J, Parkington J: Evidence for the unique function of docosahexaenoic acid during the evolution of the modern hominid brain. Lipids, 1999; 34 Suppl: S39-47
44. DeMar JC Jr, Ma K, Bell JM, Rapoport SI: Half-lives of docosahexaenoic acid in rat brain phospholipids are prolonged by 15 weeks of nutritional deprivation of n-3 polyunsaturated fatty acids. J Neurochem, 2004; 91: 1125-1137
45. Crawford MA: Docosahexaenoic acid in neural signaling systems. Nutr Health, 2006; 18: 263-276
46. Long EK, Murphy TC, Leiphon LJ, Watt J, Morrow JD, Milne GL, Howard JR, Picklo MJ Sr: Trans-4-hydroxy-2-hexenal is a neurotoxic product of docosahexaenoic (22: 6; n-3) acid oxidation. J Neurochem, 2008; 105: 714-724
47. Bradley MA, Xiong-Fister S, Markesbery WR, Lovell MA; Elevated 4-hydroxyhexenal in Alzheimer's disease (AD) progression. Neurobiol Aging. 2012; 33: 1034-1044
48. Thies F, Garry JM, Yaqoob P, Rerkasem K, Williams J, Shearman C P, Gallagher PJ, Calder PC, Grimble RF: Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial. Lancet, 2003; 361: 477-485
49. Cawood AL, Ding R, Napper FL, Young RH, Williams JA, Ward MJ, Gudmundsen O, Vige R, Payne S P, Ye S, Shearman C P, Gallagher PJ, Grimble RF, Calder PC: Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acid ethyl esters is incorporated into advanced atherosclerotic plaques and higher plaque EPA is associated with decreased plaque inflammation and increased stability. Atherosclerosis, 2010; 212: 252-259
50. Harris WS, Sands SA, Windsor SL, Ali HA, Stevens TL, Magalski A, Porter CB, Borkon AM: Omega-3 fatty acids in cardiac biopsies from heart transplantation patients: correlation with erythrocytes and response to supplementation. Circulation, 2004; 110: 1645-1649
51. Metcalf RG, James MJ, Gibson RA, Edwards JR, Stub-berfield J, Stuklis R, Roberts-Thomson K, Young GD, Cleland LG: Effects of fish-oil supplementation on myo-cardial fatty acids in humans. Am J Clin Nutr, 2007; 85: 1222-1228
52. Futata T, Asano T, Meng J, Kan K, Okumura M, Miwa H: Platelet aggregation, thromboxane A2 formation, fatty acid composition in plasma, and platelet phospho-lipids in patients with NIDDM (the effect of EPA-E). Ann Japan Soc Res Diab Complicat, 1996; 9: 31-37
53. Di Stasi D, Bernasconi R, Marchioli R, Marfisi RM, Rossi G, Tognoni G, Tacconi MT: Early modifications of fatty acid composition in plasma phospholipids, platelets and mononucleates of healthy volunteers after low doses of n-3 polyunsaturated fatty acids. Eur J Clin Pharmacol, 2004; 60: 183-190
54. Johnson RA, Lincoln FH, Nidy EG, Schneider W P, Thompson JL, Axen U: Synthesis and characterization of prostacyclin, 6-ketoprostaglandin F1.alpha., prosta-glandin I1, and prostaglandin I3. J Am Chem Soc, 1978; 100: 7690-7705
55. Whitaker MO, Wyche A, Fitzpatrick F, Sprecher H, Needleman P: Triene prostaglandins: prostaglandin D3 and icosapentaenoic acid as potential antithrombotic substances. Proc Natl Acad Sci U S A, 1979; 76: 5919-5923
56. Onodera M, Morita, Mano Y, Murota S: Differential effects of nitric oxide on the activity of prostaglandin endoperoxide H synthase-1 and -2 in vascular endothe-lial cells. Prostaglandins Leukot Essent Fatty Acids, 2000; 62: 161-167
57. Niwano K, Arai M, Tomaru K, Uchiyama T, Ohyama Y, Kurabayashi M: Transcriptional stimulation of the eNOS gene by the stable prostacyclin analogue beraprost is mediated through cAMP-responsive element in vascular endothelial cells: close link between PGI2 signal and NO pathways. Circ Res, 2003; 93: 523-530
58. Hardy P, Abran D, Hou X, Lahaie I, Peri KG, Asselin P, Varma DR, Chemtob S: A major role for prostacyclin in nitric oxide-induced ocular vasorelaxation in the piglet. Circ Res, 1998; 83: 721-729
59. Li Q, Zhang Q, Wang M, Zhao S, Ma J, Luo N, Li N, Li Y, Xu G, Li J: Eicosapentaenoic acid modifies lipid composition in caveolae and induces translocation of endothelial nitric oxide synthase. Biochimie, 2007; 89: 169-177
60. Höper MM, Voelkel NF, Bates TO, Allard JD, Horan M, Shepherd D, Tuder RM: Prostaglandins induce vascular endothelial growth factor in a human monocytic cell line and rat lungs via cAMP. Am J Respir Cell Mol Biol, 1997; 17: 748-756
61. Wheeler-Jones C, Abu-Ghazaleh R, Cospedal R, Houlis-ton RA, Martin J, Zachary I: Vascular endothelial growth factor stimulates prostacyclin production and activation of cytosolic phospholipase A2 in endothelial cells via p42/p44 mitogen-activated protein kinase. FEBS Lett, 1997; 420: 28-32
62. Santhanam AV, Smith LA, He T, Nath KA, Katusic ZS: Endothelial progenitor cells stimulate cerebrovascular production of prostacyclin by paracrine activation of cyclooxygenase-2. Circ Res, 2007; 100: 1379-1388
63. Ashton AW, Ware JA: Thromboxane A2 receptor signaling inhibits vascular endothelial growth factor-induced endothelial cell differentiation and migration. Circ Res, 2004; 95: 372-379
64. Hirata Y, Shimabukuro M, Uematsu E, Soeki T, Yamada H, Sakai Y, Nakayama M, Matsumoto K, Igarashi T, Sata M: A synthetic prostacyclin agonist with thrombox-ane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury. Eur J Pharmacol, 2012; 674: 352-358
65. Krishnamurthy P, Bird IM, Sheppard C, Magness RR: Effects of angiogenic growth factors on endothelium-derived prostacyclin production by ovine uterine and placental arteries. Prostaglandins Other Lipid Mediat, 1999; 57: 1-12
66. Tongers J, Roncalli JG, Losordo DW: Role of endothe-lial progenitor cells during ischemia-induced vasculogen-esis and collateral formation. Microvasc Res, 2010; 79: 200-206
67. He T, Lu T, d'Uscio LV, Lam CF, Lee HC, Katusic ZS: Angiogenic function of prostacyclin biosynthesis in human endothelial progenitor cells. Circ Res, 2008; 103: 80-88
68. Kawabe J, Yuhki K, Okada M, Kanno T, Yamauchi A, Tashiro N, Sasaki T, Okumura S, Nakagawa N, Aburakawa Y, Takehara N, Fujino T, Hasebe N, Naru-miya S, Ushikubi F: Prostaglandin I2 promotes recruitment of endothelial progenitor cells and limits vascular remodeling. Arterioscler Thromb Vasc Biol, 2010; 30: 464-470
69. Di Stefano R, Barsotti MC, Melillo E, Iorio M, Santoni T, Armani C, Dell'Omodarme M, Ristori C, De Caterina R, Balbarini A: The prostacyclin analogue iloprost increases circulating endothelial progenitor cells in patients with critical limb ischemia. Thromb Haemost, 2008; 100: 871-877
70. Kobayashi N, Takeshima H, Koguchi W, Ishikawa M, Sugiyama F, Onoda S, Ishimitsu T: Effect of combination therapy with bonemarrow mononuclear cells implantation and eicosapentaenoic acid on angiogenesis in myocardial ischemia. J Hypertension. 2012; 30 (e-supplement 1): 260
71. Endo M, Iwa T, Urayama H, Nagai A, Sawa S, Kuroda Y, Iida S, Hashiba A, Murakita K, Ichihashi T, Saito H, Murakami S: The multi-institutional clinical study of the effect and safety of ethyl Icosapentate on arteriosclerosis obliterans. Japanese College Angiology, 1992; 32: 233-238
72. Kanayasu T, Morita I, Nakao-Hayashi J, Asuwa N, Fujisawa C, Ishii T, Ito H, Murota S: Eicosapentaenoic acid inhibits tube formation of vascular endothelial cells in vitro. Lipids, 1991; 26: 271-276
73. Kim HJ, Vosseler CA, Weber PC, Erl W: Docosahexae-noic acid induces apoptosis in proliferating human endothelial cell. J Cell Physiol, 2005; 204: 881-888
74. Spencer L, Mann C, Metcalfe M, Webb M, Pollard C, Spencer D, Berry D, Steward W, Dennison A: The effect of omega-3 FAs on tumour angiogenesis and their therapeutic potential. Eur J Cancer, 2009; 45: 2077-86
75. Reiss AB, Edelman SD: Recent insights into the role of prostanoids in atherosclerotic vascular Disease. Curr Vasc Pharmacol, 2006; 4: 395-408
76. Numaguchi Y, Naruse K, Harada M, Osanai H, Mokuno S, Murase K, Matsui H, Toki Y, Ito T, Oku-mura K, Hayakawa T: Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointi-mal formation in rat carotid arteries after balloon injury. Arterioscler Thromb Vasc Biol, 1999; 19: 727-733
77. Cheng Y, Austin SC, Rocca B, Koller BH, Coffman TM, Grosser T, Lawson JA, FitzGerald GA: Role of prostacy-clin in the cardiovascular response to thromboxane A2. Science, 2002; 296: 539-541
78. Thomas DW, Mannon RB, Mannon PJ, Latour A, Oliver JA, Hoffman M, Smithies O, Koller BH, Coffman TM: Coagulation defects and altered hemodynamic responses in mice lacking receptors for thromboxane A2. J Clin Invest, 1998; 102: 1994-2001
79. Gabrielsen A, Qiu H, Bäck M, Hamberg M, Hemdahl AL, Agardh H, Folkersen L, Swedenborg J, Hedin U, Paulsson-Berne G, Haeggstrom JZ, Hansson GK: Thromboxane synthase expression and thromboxane A2 production in the atherosclerotic lesion. J Mol Med (Berl), 2010; 88: 795-806
80. Kobayashi T, Tahara Y, Matsumoto M, Iguchi M, Sano H, Murayama T, Arai H, Oida H, Yurugi-Kobayashi T, Yamashita JK, Katagiri H, Majima M, Yokode M, Kita T, Narumiya S: Roles of thromboxane A(2) and prostacy-clin in the development of atherosclerosis in apoE-defi-cient mice. J Clin Invest, 2004; 114: 784-794
81. Yamada H, Yoshida M, Nakano Y, Suganami T, Satoh N, Mita T, Azuma K, Itoh M, Yamamoto Y, Kamei Y, Horie M, Watada H, Ogawa Y: In vivo and in vitro inhibition of monocyte adhesion to endothelial cells and endothe-lial adhesion molecules by eicosapentaenoic acid, Arte-rioscler Thromb Vasc Biol, 2008; 28: 2173-2179
82. Collie-Duguid ES, Wahle KW: Inhibitory effect of fish oil N-3 polyunsaturated fatty acids on the expression of endothelial cell adhesion molecules, Biochem Biophys Res Commun, 1996; 220: 969-974
83. Watanabe I, Nagao K, Wang DY, Akutsu N, Shioiri K, Ohiwa K, Kikushima K, Kanmatsuse K: Usefulness of EPA-E(Eicosapentaenoic Acid Ethyl Ester) in preventing formation after vascular injury. Kokyu to Junkan, 1994; 42: 673-677
84. Nestel P, Shige H, Pomeroy S, Cehun M, Abbey M, Raederstorff D: The n-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid increase systemic arterial compliance in humans. Am J Clin Nutr, 2002; 76: 326-30
85. Coker SJ, Parratt JR, Ledingham IM, Zeitlin IJ: Throm-boxane and prostacyclin release from ischaemic myocardium in relation to arrhythmias. Nature, 1981; 291: 323-324
86. Xiao CY, Hara A, Yuhki K, Fujino T, Ma H, Okada Y, Takahata O, Yamada T, Murata T, Narumiya S, Ushi-kubi F: Roles of prostaglandin I(2) and thromboxane A(2) in cardiac ischemia-reperfusion injury: a study using mice lacking their respective receptors. Circulation, 2001; 104: 2210-2215
87. Neri Serneri GG, Modesti PA, Fortini A, Abbate R, Lombardi A, Gensini GF: Reduction in prostacyclin platelet receptors in active spontaneous angina. Lancet, 1984; 2: 838-841
88. Hara A, Yuhki K, Fujino T, Yamada T, Takayama K, Kuriyama S, Takahata O, Karibe H, Okada Y, Xiao CY, Ma H, Narumiya S, Ushikubi F: Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor. Circulation, 2005; 112: 84-92
89. Gao JY, Yasuda S, Tsuburaya R, Ito Y, Shiroto T, Hao K, Aizawa K, Kikuchi Y, Ito K, Shimokawa H: Long-term treatment with eicosapentaenoic acid ameliorates myo-cardial ischemia-reperfusion injury in pigs in vivo. -Involvement of Rho-kinase pathway inhibition. Circ J, 2011; 75: 1843-1851
90. Spector AA, Kaduce TL, Figard PH, Norton KC, Hoak JC, Czervionke RL: Eicosapentaenoic acid and prostacy-clin production by cultured human endothelial cells. J Lipid Res,1983; 24: 1595-604
91. Murota S, Morita I: Eicosapentaenoic acid. Journal of clinical and experimental medicine, 1984; 130: 787-798
92. Walsh MT, Foley J F, Kinsella BT: The alpha, but not the beta, isoform of the human thromboxane A2 receptor is a target for prostacyclin-mediated desensitization. J Biol Chem, 2000; 275: 20412-20423
93. Nishio S, Kurumatani H: Pharmacological and clinical properties of beraprost sodium, orally active pprostacy-clin analogue. Folia Pharmacol Jpn, 2001; 117: 123-130
94. Hamazaki T, Fischer S, Urakaze M, Sawazaki S, Yano S: Comparison of the urinary metabolites of prostacyclin and thromboxane of the 2- and 3-series in a Japanese fishing and a Japanese farming village. Prostaglandins, 1986; 32: 655-664
95. Grad E, Golomb M, Koroukhov N, Lawson JA, Lotan C, Fitzgerald GA, Danenberg HD: Aspirin reduces the prothrombotic activity of C-reactive protein. J Thromb Haemost, 2009; 7: 1393-1400
96. Venugopal SK, Devaraj S, Jialal I: C-reactive protein decreases prostacyclin release from human aortic endo-thelial cells. Circulation, 2003; 108: 1676-1678
97. Simpson RM, Prancan A, Izzi JM, Fiedel BA: Generation of thromboxane A2 and aorta-contracting activity from platelets stimulated with modified C-reactive protein. Immunology, 1982; 47: 193-202
98. Puccetti L, Santilli F, Pasqui AL, Lattanzio S, Liani R, Ciani F, Ferrante E, Ciabattoni G, Scarpini F, Ghezzi A, Auteri A, Davì G: Effects of atorvastatin and rosuvas-tatin on thromboxane-dependent platelet activation and oxidative stress in hypercholesterolemia. Atherosclerosis, 2011; 214: 122-128
99. Micallef MA, Munro IA, Garg ML: An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals. Eur J Clin Nutr, 2009; 63: 1154-1156
100. Satoh N, Shimatsu A, Kotani K, Sakane N, Yamada K, Suganami T, Kuzuya H, Ogawa Y: Purified eicosapentae-noic acid reduces small dense LDL, remnant lipoprotein particles, and C-reactive protein in metabolic syndrome. Diabetes Care, 2007; 30: 144-146
101. Burns T, Maciejewski SR, Hamilton WR, Zheng M, Mooss AN, Hilleman DE: Effect of omega-3 fatty acid supplementation on the arachidonic acid: eicosapentae-noic acid ratio. Pharmacotherapy, 2007; 27: 633-638