Omega-3 fatty acids decrease oxidative stress and inflammation in macrophages from patients with small abdominal aortic aneurysm

Lara T Meital,Tom G Bailey,Jonathan Golledge,Maria Perissiou,Karl Schulze,Fraser D Russell,Christopher D Askew,Rebecca Magee,Anna Kuballa,Mark T Windsor

doi:10.1038/s41598-019-49362-z

Abstract

Abdominal aortic aneurysm (AAA) is associated with inflammation and oxidative stress, the latter of which contributes to activation of macrophages, a prominent cell type in AAA. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to limit oxidative stress in animal models of AAA. The aim of this study was to evaluate the effect of the n-3 PUFA docosahexaenoic acid (DHA) on antioxidant defence in macrophages from patients with AAA. Cells were obtained from men with small AAA (diameter 3.0–4.5 cm, 75 ± 6 yr, n = 19) and age- matched male controls (72 ± 5 yr, n = 41) and incubated with DHA for 1 h before exposure to 0.1 µg/mL lipopolysaccharide (LPS) for 24 h. DHA supplementation decreased the concentration of tumour necrosis factor-α (TNF-α; control, 42.1 ± 13.6 to 5.1 ± 2.1 pg/ml, p < 0.01; AAA, 25.2 ± 9.8 to 1.9 ± 0.9 pg/ml, p < 0.01) and interleukin-6 (IL-6; control, 44.9 ± 7.7 to 5.9 ± 2.0 pg/ml, p < 0.001; AAA, 24.3 ± 5.2 to 0.5 ± 0.3 pg/ml, p < 0.001) in macrophage supernatants. DHA increased glutathione peroxidase activity (control, 3.2 ± 0.3 to 4.1 ± 0.2 nmol/min/ml/μg protein, p = 0.004; AAA, 2.3 ± 0.5 to 3.4 ± 0.5 nmol/min/ml/μg protein, p = 0.008) and heme oxygenase-1 mRNA expression (control, 1.5-fold increase, p < 0.001). The improvements in macrophage oxidative stress status serve as a stimulus for further investigation of DHA in patients with AAA.

Highlights

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (22:6n-3; DHA) and eicosapentaenoic acid (20:5n-3, EPA), have been suggested to have cardioprotective[1,2], anti-inflammatory[3], immunoregulatory[4], antioxidant[5,6] and anti-tumour activities[7]
lipopolysaccharide from Escherichia coli (LPS)-stimulated 8-isoprostane production was suppressed in macrophages from the abdominal aortic aneurysm (AAA) patient cohort, a trend towards a further decrease in 8-isoprostane levels was observed when these cells were incubated with DHA (Fig. 1B)
In AAA patient macrophages, DHA supplementation suppressed the production of TNF-α (Fig. 2B; 80 μM p = 0.006), IL-6 (Fig. 2D; 20 μM p < 0.001, 80 μM p < 0.001) and IL-10 (Fig. 2J; 20 μM p = 0.008, 80 μM p = 0.004)

Summary

Introduction

The long-chain omega-3 polyunsaturated fatty acids (n-3 PUFAs), docosahexaenoic acid (22:6n-3; DHA) and eicosapentaenoic acid (20:5n-3, EPA), have been suggested to have cardioprotective[1,2], anti-inflammatory[3], immunoregulatory[4], antioxidant[5,6] and anti-tumour activities[7] These beneficial effects on human health have been attributed to (a) competition with arachidonic acid (AA) for the enzymes involved in the biosynthesis of pro-inflammatory mediator molecules[8], (b) suppression of pro-inflammatory nuclear factor kappa B (NF-κ B) via modulation of toll-like receptor 4 (TLR4) signalling[9] and activation of peroxisome proliferator-activated receptor gamma (PPAR γ)[10], (c) activation of the G-protein-coupled receptor free fatty acid receptor 4 (FFA4, formerly GPR120)[11] and d) metabolism to pro-resolution lipid mediators (e.g. resolvins, protectins, maresins)[12,13]. The HO-1 inhibitor, SnPP (10 μM), and FFA4 receptor antagonist, AH7614 (2 μM), were used to examine mechanisms underlying n-3 PUFA effects

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