Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects

Anthony D Pisaniello; Peter J Psaltis; Peta M King; Ge Liu; Robert A Gibson; Joanne Tm Tan; MyNgan Duong; Tracy Nguyen; Christina A Bursill; Matthew I Worthley; Stephen J Nicholls; Belinda A Di Bartolo

doi:10.1016/j.atherosclerosis.2021.03.003

Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects

Atherosclerosis. 2021 May:324:27-37. doi: 10.1016/j.atherosclerosis.2021.03.003. Epub 2021 Mar 17.

Authors

Affiliations

¹ Discipline of Medicine, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute, Adelaide, Australia; School of Medicine, Johns Hopkins University, Baltimore, USA.
² Discipline of Medicine, University of Adelaide, Adelaide, Australia; South Australian Health and Medical Research Institute, Adelaide, Australia.
³ Discipline of Medicine, University of Adelaide, Adelaide, Australia.
⁴ School of Agriculture, Food and Wine, FOODPlus Research Centre, University of Adelaide, Adelaide, Australia.
⁵ GenesisCare, Adelaide, Australia.
⁶ South Australian Health and Medical Research Institute, Adelaide, Australia; Monash Cardiovascular Research Centre, Victorian Heart Institute, Monash University, Clayton, Australia.
⁷ Discipline of Medicine, University of Adelaide, Adelaide, Australia; Kolling Institute, University of Sydney, Sydney, Australia. Electronic address: Belinda.dibartolo@sydney.edu.au.

PMID: 33812168
DOI: 10.1016/j.atherosclerosis.2021.03.003

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: Animal models; Atherosclerosis; Inflammation; Lipids; Omega-3 fatty acids; Polyunsaturated fatty acids; Vascular inflammation.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Dietary Supplements
Docosahexaenoic Acids / pharmacology
Eicosapentaenoic Acid / pharmacology
Endothelial Cells*
Fatty Acids
Fatty Acids, Omega-3* / pharmacology
Fish Oils
Humans
Inflammation / prevention & control
Mice

Substances

Docosahexaenoic Acids
Eicosapentaenoic Acid
Fatty Acids
Fatty Acids, Omega-3
Fish Oils