Procoagulant Activity and Cytokine Expression in Whole Blood Cultures from Patients with Atherosclerosis Supplemented with Omega-3 Fatty Acids

Ingebjørg Seljeflot; Odd Johansen; Harald Arnesen; Jan-Bertil Eggesbø; Åse-Britt Westvik; Peter Kierulf

doi:10.1055/s-0037-1614525

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1999; 81(04): 566-570
DOI: 10.1055/s-0037-1614525

Rapid Communication

Schattauer GmbH

Procoagulant Activity and Cytokine Expression in Whole Blood Cultures from Patients with Atherosclerosis Supplemented with Omega-3 Fatty Acids

Authors

Ingebjørg Seljeflot
Odd Johansen

¹From the Research Forum, Dept of Medicine, Ullevål University Hospital, Oslo, Norway
Harald Arnesen

¹From the Research Forum, Dept of Medicine, Ullevål University Hospital, Oslo, Norway
Jan-Bertil Eggesbø

²Research and Development Group, Dept of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway
Åse-Britt Westvik

²Research and Development Group, Dept of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway
Peter Kierulf

²Research and Development Group, Dept of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway

Abstract

Summary

Omega-3 fatty acids (n-3 FA) may reduce atherogenesis and thrombosis. We investigated the effects of n-3 FAs on procoagulant activity and cytokine expression in whole blood cultures from patients with atherosclerosis. Eleven of the 23 included patients had received 5.1 g n-3 FA daily for 6 months (group I) whereas 12 patients had been on placebo (group II). All patients were then given 5.1g n-3 FA daily for another 4 weeks.

At baseline significantly lower levels of LPS-induced prothrombin fragment₁₊₂ were found in group I (p = 0.010), this difference being eliminated after 4 weeks. Il-6 and TNF_αwere significantly higher at baseline in group I and the differences in changes from baseline between the groups were statistically highly significant with increasing values in group II (Il-6 p = 0.001, TNF_αp = 0.002).

The present results indicate a reduction in pro-thrombotic potential in patients receiving highly concentrated n-3 FA, whereas some pro-inflammatory responses might be adverse.

Full Text

References

References
1 Kinsella JE. Effects of polyunsaturated fatty acids on factors related to cardiovascular disease. Am J Cardiol 1987; 60: 23G-32G.
2 Leaf A, Weber PC. Cardiovascular effects of n-3 fatty acids. N Eng J Med 1988; 318: 549-57.
3 Eritsland J, Arnesen H, Grønseth K Fjeld NB, Abdelnoor A. Effect of supplementation with n-3 fatty acids on coronary artery bypass graft patency. Am J Cardiol 1996; 77: 31-8.
4 Harris WS. Dietary fish oil and blood lipids. Current Opinion in Lipidology 1996; 7: 3-7.
5 Bønaa KH, Bjerve KS, Straume B, Gram IT, Thelle D. Effects of eicosapentaenoic and docosahexaenoic acids on blood pressure in hypertension. N Engl J Med 1990; 322: 795-801.
6 Kristensen SD, Schmidt EB, Dyerberg J. Dietary supplementation with n-3 polyunsaturated fatty acids and human platelet function: a review with particular emphasis on implications for cardiovascular disease. J Intern Med 1989; 225: 141-50.
7 Muller AD, van Houwelingen AC, van Dam-Mieras MCE, Bas MB, Hornstra G. Effect of a moderate fish intake on haemostatic parameters in healthy males. Thromb Haemost 1989; 61: 468-73.
8 Emeis JJ, van Houwelingen AC, van den Hoogen CM, Hornstra G. A moderate fish intake increases plasminogen activator inhibitor type-1 in human volunteers. Blood 1989; 74: 233-7.
9 Eritsland J, Arnesen H, Seljeflot I, Kierulf P. Long-term effect of n-3 polyunsaturated n-3 Fatty acids on haemostatic variables and bleeding episodes in patients with coronary artery disease. Blood Coagulation Fibrinolysis 1995; 6: 17-22.
10 Fisher M, Levine PH, Leaf A. n-3 fatty acids and cellular aspects of atherosclerosis. Arch Intern Med 1989; 149: 1726-8.
11 Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 1993; 362: 801-9.
12 Ray A, Tatter SB, Santhanam V, Helfgott DC, May LT, Sehgal PB. Regulation of expression of interleukin-6. Ann NY Acad Sci 1989; 557: 353-61.
13 Osnes LTN, Westvik Å B, Kierulf P. Procoagulant and profibrinolytic activities of cryopreserved human monocytes. Thromb Res 1994; 76: 373-83.
14 Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JWM, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaffer EJ, Wolff SM, Dinarello CA. The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 1989; 320: 265-71.
15 Endres S, von Schacky C. n-3 polyunsaturated fatty acids and human cytokine synthesis. Current Opinion in Lipidology 1996; 7: 48-52.
16 De Caterina R, Libby P. Control of endothelial leucocyte adhesion molecules by fatty acids. Lipids 1996; 31: S57-S63.
17 Eritsland J, Seljeflot I, Arnesen H, Westvik Å B, Kierulf P. Effect of longterm, moderate-dose supplementation with omega-3 fatty acid on monocyte procoagulant activity and release of interleukin-6 in patients with coronary artery disease. Thromb Res 1995; 77: 337-46.
18 Schmidt EB, Varming K, Møller JM, Bulow Pedersen I, Madsen P, Dyerberg J. No effect of a very low dose of n-3 fatty acids on monocyte function in healthy humans. Scand J Lab Clin Invest 1996; 56: 87-92.
19 van Deuren M, van der Ven-Jongekrijg J, Keuter M, Demacker PNM, van der Meer JWM. Cytokine production in whole blood cultures. J Intern Fed Clin Chem 1993; 5: 216-21.
20 Eggesbø JB, Hjermann I, Høstmark AT, Joø GB, Kierulf P. Lipopolysaccharide-induced monocyte procoagulant activity, fibrinopeptide A, and PAI-1 levels in persons with high or low levels of HDL-lipoprotein. Thromb Res 1993; 70: 161-71.
21 Johansen O, Brekke M, Seljeflot I, Abdelnoor M, Arnesen H. n-3 fatty acids do not prevent restenosis after coronary angioplasty. Eur Heart J 1997; 18 Suppl 3591.
22 Brandtzæg P, Kierulf P, Gaustad P, Skulberg A, Bruun JN, Halvorsen S, Sørensen E. Plasma endotoxin as a predictor of multiple organ failure and death in systemic meningococcal disease. J Inf Dis 1989; 159 (02) 195-204.
23 Skjønsberg OH, Kierulf P, Fagerhol M, Godal HC. Thrombin generation during collection and storage of blood. Vox Sang 1986; 50: 33-7.
24 Brude IR, Drevon CA, Hjermann I, Seljeflot I, Lund-Katz S, Saarem K, Sandstad B, Solvoll K, Halvorsen B, Arnesen H, Nenseter MS. Peroxidation of low density lipoprotein from male smokers with combined hyper-lipidemia supplied with omega-3 fatty acids and antioxidants. Arterioscler Thromb Vasc Biol 1997; 17: 2576-88.
25 Marangoni F, Angeli MT, Colli S, Elegini S, Tremoli S, Sirtori CR, Galli C. Changes in n-3 and n-6 fatty acids in plasma and circulatory cells of normal subjects, after prolonged administration of 20: 5 (EPA) and 22: 6 (DHA) ethyl esters and prolonged washout. Biochem Biophys Acta 1993; 1210: 55-62.
26 Hansen JB, Olsen JO, Wilsgård L, Østerud B. Effects of dietary supplementation with cod liver oil on monocyte thromboplastin synthesis, coagulation and fibrinolysis. J Intern Med 1989; 225 (Suppl. 01) Suppl 133-9.
27 Kierulf P, Andersen Å BW. Lipopolysaccharide-instructed, cryopreserved, human monocytes sequentially convert plasma fibrinogen to fibrin and lyse the fibrin formed. Pathobiology 1991; 59: 197-9.
28 Abbate R, Gori AM, Martini F, Brunelli T, Filippini M, Francalanci I, Paniccia R, Prisco D, Gensisni GF, Serneri GGN. n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production. Prostaglandins, Leukotrienes and Essential Fatty Acids 1996; 54: 439-44.
29 Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Eng J Med 1989; 320: 915-24.
30 Lussier-Cacan S, Dubreuil-Quidoz S, Roederer G, Leboeuf N, Boulet L, de Langavant GC, Davignon J, Naruszewicz M. Influence of probucol on enhanced LDL oxidation after fish oil treatment of hypertriglyceridemic patients. Arterioscle Thromb 1993; 13: 1790-7.
31 Frankel EN, Parks EJ, Xu R, Schneeman BO, Davies PA, German JB. Effects of n-3 fatty acid-rich fish oil supplementation on the oxidation of low density lipoproteins. Lipids 1994; 29: 233-6.
32 Seljeflot I, Arnesen H, Brude IR, Nenseter MS, Drevon CR, Hjermann I. Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers. Eur J Clin Invest 1998; 28: 629-35.
33 Hau MF, Smelt AHM, Bindels AJGH, Sijbrands EJG, Van der Laarse A, Onkenhout W, Duyvenvoorde W, Princen HMG. Effects of fish oil oxidation resistance of VLDL in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol 1996; 16: 1197-202.
34 Collins T. Biology of disease: endothelial nuclear factor-kB and the initiation of the atherosclerotic lesion. Lab Invest 1993; 68: 499-508.