Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/130593
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Type: Journal article
Title: Omega-3 fatty acids ameliorate vascular inflammation: a rationale for their atheroprotective effects
Author: Pisaniello, A.D.
Psaltis, P.J.
King, P.M.
Liu, G.
Gibson, R.A.
Tan, J.T.M.
Duong, M.
Nguyen, T.
Bursill, C.A.
Worthley, M.I.
Nicholls, S.J.
Di Bartolo, B.A.
Citation: Atherosclerosis, 2021; 324:27-37
Publisher: Elsevier
Issue Date: 2021
ISSN: 0021-9150
1879-1484
Statement of
Responsibility: 
Anthony D.Pisaniello, Peter J.Psaltis, Peta M.King, Ge Liu, Robert A.Gibson, Joanne TM.Tan ... et al.
Abstract: Background and aims: Clinical trials have demonstrated reductions in major adverse cardiovascular events with purified high-dose eicosapentaenoic acid (EPA), independent of effects on lipids. We aimed to investigate whether omega-3 fatty acids reduce vascular inflammation, a critical mediator of atherosclerosis, and hypothesised that EPA is superior to docosahexaenoic acid (DHA). Methods: In a double-blind randomised controlled trial and cell-culture study, 40 healthy volunteers were supplemented with 4 g daily of either EPA, DHA, fish oil (2:1 EPA:DHA), or placebo for 30 days. Serum was incubated with TNF-stimulated human umbilical vein endothelial cells (HUVECs), and markers of acute vascular inflammation (AVI) were measured. The effects of EPA, DHA (600 mg/kg/day), olive oil, or no treatment were also measured in preclinical models of [1] AVI using a periarterial collar (C57Bl/6J; n = 40 mice) and [2] atherosclerosis where ApoE−/− mice (n = 40) were fed a 16-week atherogenic diet. Results: EPA supplementation reduced expression of C–C motif chemokine ligand 2 (CCL2) by 25% compared to placebo (p = 0.03). In the AVI model, EPA reduced vascular expression of VCAM1 by 43% (p = 0.02) and CCL2 by 41% (p = 0.03). Significant inverse correlations were observed between EPA levels and vascular expression of VCAM1 (r = −0.56, p = 0.001) and CCL2 (r = −0.56, p = 0.001). In ApoE−/- mice, EPA reduced aortic expression of Il1b by 44% (p = 0.04) and Tnf by 49% (p = 0.04), with similar inverse correlations between EPA levels and both Il1b (r = −0.63, p = 0.009) and Tnf (r = −0.50, p = 0.04). Conclusions: Supplementation with EPA, more so than DHA, ameliorates acute and chronic vascular inflammation, providing a rationale for the cardiovascular benefit observed with high dose omega-3 fatty acid administration.
Keywords: Omega-3 fatty acids; polyunsaturated fatty acids; lipids; atherosclerosis; vascular inflammation; inflammation; animal models
Rights: © 2021 Elsevier B.V. All rights reserved.
RMID: 1000039546
DOI: 10.1016/j.atherosclerosis.2021.03.003
Grant ID: http://purl.org/au-research/grants/nhmrc/CDF1161506
Appears in Collections:Medicine publications

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