Eicosapentaenoic Acid (EPA) Reduces Cardiovascular Events: Relationship with the EPA/Arachidonic Acid Ratio

Journal of Atherosclerosis and Thrombosis - Tập 20 Số 12 - Trang 861-877 - 2013
Haruo Ohnishi1, Yasushi Saitō2
1Mochida Pharmaceutical Co. Ltd.
2Chiba University Graduate School of Medicine

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1) Gorjão R, Azevedo-Martins AK, Rodrigues HG, Abdulkader 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, interconversion, 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 JP, 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: Responses to “ 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 ingestion 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 AP, Marchioli R, Barlera S, Franzosi MG, Latini R, Lucci D, Nicolosi GL, Porcu M, Tognoni G: 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

20) Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada 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 endpoint 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, Spiegelman 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 lysophospholipids. 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 neutrophils. 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 phosphatidylinositol and phosphatidylcholine in thrombinstimulated 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-acylglycerophosphorylcholine acyltransferase and acyl-CoA synthetase 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: Phospholipid composition of cultured human endothelial cells. Lipids, 1992; 27: 150-153

34) Jamin SP, 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 permeabilized with saponin. Biochim Biophys Acta, 1990; 1054: 159-168

36) Arterburn LM, Hall EB, Oken H: Distribution, interconversion, 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 triglyceridemia. Lipids, 1998; 33: 131-138

38) Mori TA, Burke V, Puddey IB, Watts GF, O’Neal DN, Best JD, Beilin LJ: Purified eicosapentaenoic and docosahexaenoic acids have differential effects on serum lipids 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 Atheroscler 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 JP, 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-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

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-hydroxy2-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 CP, 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 SP, Ye S, Shearman CP, Gallagher PJ, Grimble RF, Calder PC: Eicosapentaenoic acid (EPA) from highly concentrated n-3 fatty acidethyl 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, Stubberfield J, Stuklis R, Roberts-Thomson K, Young GD, Cleland LG: Effects of fish-oil supplementation on myocardial 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 phospholipids 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 WP, Thompson JL, Axen U: Synthesis and characterization of prostacyclin, 6-ketoprostaglandin F1.alpha., prostaglandin 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 endothelial 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, Houliston 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 thromboxane 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 endotheliumderived 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 endothelial progenitor cells during ischemia-induced vasculogenesis 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, Narumiya 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, Fuji sawa 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: Docosahexaenoic 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: 2077-2086

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, Okumura K, Hayakawa T: Prostacyclin synthase gene transfer accelerates reendothelialization and inhibits neointimal 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 prostacyclin 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 prostacyclin in the development of atherosclerosis in apoE-deficient 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 endothelial adhesion molecules by eicosapentaenoic acid, Arterioscler 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: Thromboxane 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, Ushikubi 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 myocardial 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 prostacyclin 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 JF, 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 pprostacyclin 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 endothelial 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 rosuvastatin 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 eicosapentaenoic 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: eicosapentaenoic acid ratio. Pharmacotherapy, 2007; 27: 633-638