Omega-3 fatty acids ameliorate vascular inflammation: A rationale for their atheroprotective effects. (May 2021)

• Record Type: Journal Article
• Authors: Pisaniello, Anthony D.; Psaltis, Peter J.; King, Peta M.; Liu, Ge; Gibson, Robert A.; Tan, Joanne TM.; Duong, MyNgan; Nguyen, Tracy; Bursill, Christina A.; Worthley, Matthew I.; Nicholls, Stephen J.; Di Bartolo, Belinda A.
• Is Part Of: Atherosclerosis. Volume 324(2021)
• Page Start: 27
• Page End: 37
• Publication Date: 2021-05
• Subjects: Omega-3 fatty acids -- Polyunsaturated fatty acids -- Lipids -- Atherosclerosis -- Vascular inflammation -- Inflammation -- Animal models; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2021.03.003
• Languages: English
• ISSNs: 0021-9150

Abstract

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. Graphical abstract: Image 1 Highlights: Eicosapentaenoic acid (EPA) reduced expression of markers of acute vascular inflammation after inflammatory stimuli, in in vitro and in vivo models. EPA reduced expression of markers of chronic vascular inflammation but not plaque burden, in an atherogenic mouse model. Blood EPA and docosahexaenoic acid (DHA) levels correlated inversely with markers of vascular inflammation, with EPA having a stronger correlation.