Abstract
Background
Diet is known to have an important impact on cardiovascular health. n-3 Fatty acids
(FAs), found in high quantity in fish oil, have demonstrated beneficial effects in
patients with coronary artery disease. The role of n-6 FAs remains more controversial.
The objective of this study was to examine the effect of arachidonic acid (AA), an
n-6 FA, and eicosapentanoic acid (EPA), an n-3 FA, on the interaction between monocytes
and endothelial cells (ECs).
Design
We used a cellular model of ECs (EA.hy.926) and monocytes (human leukemic myelomonocytic
U937). Confluent ECs were treated with AA or EPA, in the presence of tumor necrosis
factor-alpha (TNF-α) or vehicle alone for either 4 or 24 h. Adhesion of monocytes to the endothelial monolayer was performed. For gene expression,
reverse transcription, followed by real-time quantitative polymerase chain reaction,
was performed.
Results
There was a significant increase in adhesion of monocytes to the endothelial monolayer
in the presence of n-6 FAs, both in the presence and in the absence of TNF-α at 4 and
24 h. The adhesion of monocytes to the endothelial monolayer was decreased with n-3 FAs
at 24 h. Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-Selectin,
Interleukin 6, and TNF-α were significantly increased in ECs treated with n-6 FAs.
Conclusions
We conclude that AA increases inflammation and enhances the ability of ECs to bind
monocytes in vitro. EPA leads to a decrease in the ability of EA.hy.926 to bind monocytes, although
the effect appears more modest. Taken together, these data indicate that the n-6 FA
AA could potentiate inflammation and early events of atherosclerosis.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Surgical ResearchAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART).Lancet. 1989; 2: 757
- 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
- Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis.Lancet. 2007; 369: 1090
- Polyunsaturated fatty acids and peripheral artery disease.Vasc Med. 2012; 17: 51
- Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review.Clin Cardiol. 2009; 32: 365
- Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules.Lipids Health Dis. 2008; 7: 37
- n-6 fatty acid-specific and mixed polyunsaturate dietary interventions have different effects on CHD risk: a meta-analysis of randomised controlled trials.Br J Nutr. 2010; 104: 1586
- Inflammation, atherosclerosis, and coronary artery disease.N Engl J Med. 2005; 352: 1685
- Innate and adaptive immunity in the pathogenesis of atherosclerosis.Circ Res. 2002; 91: 281
- Role of monocytes in atherogenesis.Physiol Rev. 2003; 83: 1069
- Fatty acids and signalling in endothelial cells.Prostaglandins Leukot Essent Fatty Acids. 2010; 82: 189
- Permanent cell line expressing human factor VIII-related antigen established by hybridization.Proc Natl Acad Sci U S A. 1983; 80: 3734
- Establishment and characterization of a human histiocytic lymphoma cell line (U-937).Int J Cancer. 1976; 17: 565
- A non-isotopic, highly sensitive, fluorimetric, cell-cell adhesion microplate assay using calcein AM-labeled lymphocytes.J Immunol Methods. 1995; 178: 41
- A short pulse of mechanical force induces gene expression and growth in MC3T3-E1 osteoblasts via an ERK 1/2 pathway.J Bone Miner Res. 2003; 18: 58
- Key gravity-sensitive signaling pathways drive T cell activation.Faseb J. 2005; 19: 2020
- Early immune response and regulation of IL-2 receptor subunits.Cell Signal. 2005; 17: 1111
- The omega-3 fatty acid nutritional landscape: health benefits and sources.J Nutr. 2012; 142: 587S
- Effect of fatty acids on expression of endothelial leukocyte adhesion molecules.Eur J Nutr. 2003; 42: 224
- Lack of proinflammatory effects of free fatty acids on human umbilical cord vein endothelial cells and leukocytes.Acta Obstet Gynecol Scand. 2005; 84: 672
- Linoleic acid-stimulated vascular adhesion molecule-1 expression in endothelial cells depends on nuclear factor-kappaB activation.Metabolism. 2002; 51: 327
- Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells.Am J Clin Nutr. 2002; 75: 119
- Quercetin protects against linoleic acid-induced porcine endothelial cell dysfunction.J Nutr. 2004; 134: 771
- Use of nonsteroidal anti-inflammatory drugs in patients with cardiovascular disease: a cautionary tale.Cardiol Rev. 2010; 18: 204
- Omega-3 fatty acids and inflammation: novel interactions reveal a new step in neutrophil recruitment.PLoS Biol. 2009; 7: e1000177
- Eicosapentaenoic acid and prevention of thrombosis and atherosclerosis?.Lancet. 1978; 2: 117
- The role of fatty acids and caveolin-1 in tumor necrosis factor alpha-induced endothelial cell activation.Metabolism. 2008; 57: 1328
- Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells.Invest Ophthalmol Vis Sci. 2005; 46: 4342
- Regulation of adhesion molecule expression in human endothelial and smooth muscle cells by omega-3 fatty acids and conjugated linoleic acids: involvement of the transcription factor NF-kappaB?.Prostaglandins Leukot Essent Fatty Acids. 2008; 78: 33
- Oxidized omega-3 fatty acids in fish oil inhibit leukocyte-endothelial interactions through activation of PPAR alpha.Blood. 2002; 100: 1340
- Docosahexaenoic acid selectively attenuates induction of vascular cell adhesion molecule-1 and subsequent monocytic cell adhesion to human endothelial cells stimulated by tumor necrosis factor-alpha.Arterioscler Thromb Vasc Biol. 1995; 15: 622
- Control of endothelial leukocyte adhesion molecules by fatty acids.Lipids. 1996; 31: S57
- The omega-3 fatty acid docosahexaenoate reduces cytokine-induced expression of proatherogenic and proinflammatory proteins in human endothelial cells.Arterioscler Thromb. 1994; 14: 1829
- Omega-3 fatty acids and the regulation of expression of endothelial pro-atherogenic and pro-inflammatory genes.J Membr Biol. 2005; 206: 103
- 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
- Docosahexaenoic acid attenuates VCAM-1 expression and NF-kappaB activation in TNF-alpha-treated human aortic endothelial cells.J Nutr Biochem. 2011; 22: 187
- Omega-3 fatty acids and endothelial leukocyte adhesion molecules.Prostaglandins Leukot Essent Fatty Acids. 1995; 52: 191
- Omega-3 fatty acids suppress monocyte adhesion to human endothelial cells: role of endothelial PAF generation.Am J Physiol Heart Circ Physiol. 2002; 283: H811
- Fatty acids differentially influence phosphatidylinositol 3-kinase signal transduction in endothelial cells: impact on adhesion and apoptosis.Atherosclerosis. 2008; 197: 630
- Association of n-3 polyunsaturated fatty acids with stability of atherosclerotic plaques: a randomised controlled trial.Lancet. 2003; 361: 477
- Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee.Circulation. 2006; 114: 82
- Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease.Circulation. 2002; 106: 2747
- 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
- Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism; Council on Cardiovascular Nursing; and Council on Epidemiology and Prevention.Circulation. 2009; 119: 902
- Too much linoleic acid promotes inflammation-doesn't it?.Prostaglandins Leukot Essent Fatty Acids. 2008; 79: 173
- The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases.Exp Biol Med (Maywood). 2008; 233: 674
- The debate about n-6 polyunsaturated fatty acid recommendations for cardiovascular health.J Am Diet Assoc. 2010; 110: 201
- Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects.Am J Clin Nutr. 2006; 83: 575
- Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers.J Clin Endocrinol Metab. 2006; 91: 439
- Arachidonate 5-lipoxygenase promoter genotype, dietary arachidonic acid, and atherosclerosis.N Engl J Med. 2004; 350: 29
- Lower eicosapentaenoic acid and higher arachidonic acid levels in Sera of young adults in the Netherlands than in Japan.Environ Health Prev Med. 2000; 5: 60
Article info
Publication history
Published online: April 30, 2012
Received in revised form:
March 21,
2012
Received:
February 3,
2012
Identification
Copyright
Published by Elsevier Inc.