Anthony D Pisaniello1, Peter J Psaltis2, Peta M King3, Ge Liu4, Robert A Gibson4, Joanne Tm Tan2, MyNgan Duong5, Tracy Nguyen5, Christina A Bursill2, Matthew I Worthley2, Stephen J Nicholls6, Belinda A Di Bartolo7. 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.
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.
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.
Authors: Mariely Mendes Furtado; Joana Érica Lima Rocha; Ana Victória da Silva Mendes; Renato Sampaio Mello Neto; Ana Karolinne da Silva Brito; José Otávio Carvalho Sena de Almeida; Emerson Iuri Rodrigues Queiroz; José Vinícius de Sousa França; Ana Lina de Carvalho Cunha Sales; Andreanne Gomes Vasconcelos; Wanessa Felix Cabral; Luana de Oliveira Lopes; Iolanda Souza do Carmo; Selma Aparecida Souza Kückelhaus; José Roberto de Souza de Almeida Leite; Adriana Maria Viana Nunes; Marcia Dos Santos Rizzo; Antônia Maria das Graças Lopes Citó; Ana Karina Marques Fortes Lustosa; Massimo Lucarini; Alessandra Durazzo; Maria do Carmo de Carvalho E Martins; Daniel Dias Rufino Arcanjo Journal: Biology (Basel) Date: 2022-01-27