Parallel decrease of tissue factor surface exposure and increase of tissue factor microparticle release by the n-3 fatty acid docosahexaenoate in endothelial cells

Serena Del Turco; Giuseppina Basta; Guido Lazzerini; Monica Evangelista; Giuseppe Rainaldi; Piero Tanganelli; Marina Camera; Elena Tremoli; Raffaele De Caterina

doi:10.1160/TH06-07-0402

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2007; 98(01): 210-219
DOI: 10.1160/TH06-07-0402

Endothelium and Vascular Development

Schattauer GmbH

Parallel decrease of tissue factor surface exposure and increase of tissue factor microparticle release by the n-3 fatty acid docosahexaenoate in endothelial cells

Serena Del Turco

¹C.N.R. Institute of Clinical Physiology, Pisa

²Institute of Pathology, the University of Siena, Siena

,

Giuseppina Basta

¹C.N.R. Institute of Clinical Physiology, Pisa

,

Guido Lazzerini

¹C.N.R. Institute of Clinical Physiology, Pisa

,

Monica Evangelista

¹C.N.R. Institute of Clinical Physiology, Pisa

,

Giuseppe Rainaldi

¹C.N.R. Institute of Clinical Physiology, Pisa

,

Piero Tanganelli

²Institute of Pathology, the University of Siena, Siena

,

Marina Camera

³Institute of Pharmacological Sciences, University of Milan, Milan

,

Elena Tremoli

³Institute of Pharmacological Sciences, University of Milan, Milan

,

Raffaele De Caterina

¹C.N.R. Institute of Clinical Physiology, Pisa

⁴Chair of Cardiology and Center of Excellence on Aging, “G. d’Annunzio” University, Chieti; Italy

› Author Affiliations

Abstract

Summary

Tissue factor (TF) is expressed on the endothelium in response to inflammatory mediators, giving endothelial cells a pro-thrombotic phenotype. Since fish-derived n-3 fatty acids (FA) have been associated with reduced incidence of myocardial infarction, we investigated the endothelial effects of the most abundant n-3 FA, docosahexaenoate (DHA), on TF expression. Human umbilical vein endothelial cells were pre-incubated with DHA (or stearate and arachidonate as controls) for 48–72 hours, and then stimulated with bacterial lipopolysaccharide (LPS) or tumor necrosis factor-α. Pre-incubation of endothelial cells with DHA (but not stearate or arachidonate) concentration-dependently reduced surface protein exposure, independent of TF mRNA or total protein expression regulation. Conversely, DHA treatment in conjunction with activating stimuli, induced the release of endothelial TF-exposing microparticles from endothelial cells,quantitatively accounting for the decreasedTF cell surface exposure. In conclusion,DHA treatment, with a time-course consistent with its incorporation in membrane phospholipids, increases the release of TF-exposing microparticles from endothelial cells, accounting for decreased endothelial cell TF surface exposure, thus potentially modifying the overall endothelial control of microparticle-related effects.

Keywords

Endothelial cells - microparticles - omega-3 fatty acids - n-3 fatty acids - procoagulant activity - tissue factor

Full Text

References

References
1 Steffel J, Luscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation 2006; 113: 722-731.
2 Szotowski B, Antoniak S, Poller W. et al. Procoagulant soluble tissue factor is released from endothelial cells in response to inflammatory cytokines. Circ Res 2005; 96: 1233-1239.
3 Camerer E, Kolsto AB, Prydz H. Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res 1996; 81: 1-41.
4 Muller I, Klocke A, Alex M. et al. Intravascular tissue factor initiates coagulation via circulating microve-sicles and platelets. FASEB J 2003; 17: 476-478.
5 Rauch U, Nemerson Y. Tissue factor, the blood, and the arterial wall. Trends Cardiovasc Med 2000; 10: 139-143.
6 Berckmans RJ, Neiuwland R, Boing AN. et al. Cell-derived microparticles circulate in healthy humans and support low grade thrombin generation. Thromb Haemost 2001; 85: 639-646.
7 Combes V, Simon AC, Grau GE. et al. In vitro generation of endothelial microparticles and possible pro-thrombotic activity in patients with lupus anticoagulant. J Clin Invest 1999; 104: 93-102.
8 Mallat Z, Benamer H, Hugel B. et al. Elevated levels of shed membrane microparticles with procoagulant potential in the peripheral circulating blood of patients with acute coronary syndromes. Circulation 2000; 101: 841-843.
9 GISSI Prevenzione Group.. Dietary supplementation with n-3 polyunsaturated 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.
10 Albert CM, Campos H, Stampfer MJ. et al. Blood levels of long-chain n-3 fatty acids and the risk of sudden death. N Engl J Med 2002; 346: 1113-1118.
11 de Lorgeril M, Salen P, Defaye P. et al. Dietary prevention of sudden cardiac death. Eur Heart J 2002; 23: 277-285.
12 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.
13 Agren JJ, Vaisanen S, Hanninen O. et al. Hemostatic factors and platelet aggregation after a fish-enriched diet or fish oil or docosahexaenoic acid supplementation. Prostaglandins Leukot Essent Fatty Acids 1997; 57: 419-421.
14 Conquer JA, Cheryk LA, Chan E. et al. Effect of supplementation with dietary seal oil on selected cardiovascular risk factors and hemostatic variables in healthy male subjects. Thromb Res 1999; 96: 239-250.
15 Schmidt EB, Arnesen H, Christensen JH. et al. Marinen-3 polyunsaturated fatty acids and coronary heart disease: Part II, clinical trials and recommendations. Thromb Res 2005; 115: 257-262.
16 Schmidt EB, Arnesen H, De Caterina R. et al. Marinen-3 polyunsaturated fatty acids and coronary heart disease. Part I, Background, epidemiology, animal data, effects on risk factors and safety. Thromb Res 2005; 115: 163-170.
17 Muller AD, van Houwelingen AC, van Dam-Mieras MC. et al. Effect of a moderate fish intake on haemostatic parameters in healthy males. Thromb Haemost 1989; 61: 468-473.
18 Tremoli E, Eligini S, Colli S. et al. n-3 fatty acid ethyl esterad ministration to healthy subjects and to hy-pertriglyceridemic patients reduces tissue factor activity in adherent monocytes. Arterioscler Thromb 1994; 14: 1600-1608.
19 De Caterina R, Cybulsky MI, Clinton SK. et al. The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells. Arterioscler Thromb 1994; 14: 1829-1836.
20 De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr 2000; 71: 213S-23S.
21 Massaro M, Basta G, Lazzerini G. et al. Quenching of intracellular ROS generation as a mechanism for oleate-induced reduction of endothelial activation and early atherogenesis. Thromb Haemost 2002; 88: 335-344.
22 Massaro M, Habib A, Lubrano L. et al. The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H)oxidase and PKCepsilon inhibition. Proc Natl Acad Sci USA 2006; 103: 15184-15189.
23 Jain SK. Hyperglycemia can cause membrane lipid peroxidation and osmotic fragility in human red blood cells. J Biol Chem 1989; 264: 21340-21345.
24 De Caterina R, Tanaka H, Nakagawa T. et al. The direct effect of injectable cyclosporine and its vehicle, cremophor, on endothelial vascular cell adhesion molecule-1 expression. Ricinoleic acid inhibits coronary artery endothelial activation. Transplantation 1995; 60: 270-275.
25 Pober JS, Gimbrone Jr., MA, Lapierre LA. et al. Overlapping patterns of activation of human endothelial cells by interleukin 1, tumor necrosis factor, and immune interferon. J Immunol 1986; 137: 1893-1896.
26 Camera M, Giesen PL, Fallon J. et al. Cooperation between VEGF and TNF-alpha is necessary for exposure of active tissue factor on the surface of human endothelial cells. Arterioscler Thromb Vasc Biol 1999; 19: 531-537.
27 Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem 1987; 162: 156-159.
28 Colucci M, Balconi G, Lorenzet R. et al. Cultured human endothelial cells generate tissue factor in response to endotoxin. J Clin Invest 1983; 71: 1893-1896.
29 Bevilacqua MP, Pober JS, Majeau GR. et al. Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci USA 1986; 83: 4533-4537.
30 De Caterina R, Bernini W, Carluccio MA. et al. Structural requirements for inhibition of cytokine-induced endothelial activation by unsaturated fatty acids. J Lipid Res 1998; 39: 1062-1070.
31 Thies F, Miles EA, Nebe-von-Caron G. et al. Influence of dietary supplementation with long-chain n-3 or n-6 polyunsaturated fatty acids on blood inflammatory cell populations and functions and on plasma soluble adhesion molecules in healthy adults. Lipids 2001; 36: 1183-1193.
32 Burr ML, Fehily AM, Gilbert JF. et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989; 2: 757-761.
33 Maziere C, Conte MA, Degonville J. et al. Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NFkappaB. Biochem Biophys Res Commun 1999; 265: 116-122.
34 Diep QN, Touyz RM, Schiffrin EL. Docosahexaenoic acid, a peroxisome proliferator-activated receptor-alpha ligand, induces apoptosis in vasculars mooth muscle cells by stimulation of p38 mitogen-activated protein kinase. Hypertension 2000; 36: 851-855.
35 Kim HJ, Vosseler CA, Weber PC. et al. Docosahexaenoic acid induces apoptosis in proliferating human endothelial cells. J Cell Physiol 2005; 204: 881-888.
36 Chu AJ, Walton MA, Prasad JK. et al. Blockade by polyunsaturated n-3 fatty acids of endotoxin-induced monocytic tissue factor activation is mediated by the depressed receptor expression in THP-1 cells. J Surg Res 1999; 87: 217-224.
37 Lindmark E, Tenno T, Siegbahn A. Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression. Arterioscler Thromb Vasc Biol 2000; 20: 2322-2328.
38 Schecter AD, Giesen PL, Taby O. et al. Tissue factor expression in human arterial smooth muscle cells. TF is present in three cellular pools after growth factor stimulation. J Clin Invest 1997; 100: 2276-2285.
39 Mulder AB, Smit JW, Bom VJ. et al. Association of smooth muscle cell tissue factor with caveolae. Blood 1996; 88: 1306-1313.
40 Kagawa H, Komiyama Y, Nakamura S. et al. Expression of functional tissue factor on smallvesicles of lipopolysaccharide-stimulated human vascular endothelial cells. Thromb Res 1998; 91: 297-304.
41 Abid Hussein MN, Meesters EW, Osmanovic N. et al. Antigenic characterization of endothelial cell-derived microparticles and their detection ex vivo. J Thromb Haemost 2003; 1: 2434-2443.
42 Martinez MC, Tesse A, Zobairi F. et al. Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 2005; 288: H1004-1009.
43 Serhan CN, Arita M, Hong S. et al. Resolvins, docosatrienes, and neuroprotectins, novel omega-3-derived mediators, and their endogenous aspirin-triggered epimers. Lipids 2004; 39: 1125-1132.
44 Zamaria N. Alteration of polyunsaturated fatty acid status and metabolism in health and disease. Reprod Nutr Dev 2004; 44: 273-282.
45 Van Wijk MJ, Van Bavel E, Sturk A. et al. Microparticles in cardiovascular diseases. Cardiovasc Res 2003; 59: 277-287.
46 Grundt H, Nilsen DW, Hetland O. et al. Athero-thrombogenic risk modulation by n-3 fatty acids was not associated with changes in homocysteine in subjects with combined hyperlipidaemia. Thromb Haemost 1999; 81: 561-565.
47 Freyssinet JM. Cellular microparticles: what are they bad or good for?. J Thromb Haemost 2003; 1: 1655-1662.