The resolution of inflammation through omega-3 fatty acids in atherosclerosis, intimal hyperplasia, and vascular calcification

Miguel Carracedo,Gonzalo Artiach,Hildur Arnardottir,Magnus Bäck

doi:10.1007/s00281-019-00767-y

Miguel Carracedo, Gonzalo Artiach + Show 2 more

Open Access

https://doi.org/10.1007/s00281-019-00767-y

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Abstract

Omega-3 fatty acids serve as the substrate for the formation of a group of lipid mediators that mediate the resolution of inflammation. The cardiovascular inflammatory response in atherosclerosis and vascular injury is characterized by a failure in the resolution of inflammation, resulting in a chronic inflammatory response. The proresolving lipid mediator resolvin E1 (RvE1) is formed by enzymatic conversion of the omega-3 fatty acid eicosapentaenoic acid (EPA), and signals resolution of inflammation through its receptor ChemR23. Importantly, the resolution of cardiovascular inflammation is an active, multifactorial process that involves modulation of the immune response, direct actions on the vascular wall, as well as close interactions between macrophages and vascular smooth muscle cells. Promoting anti-atherogenic signalling through the stimulation of endogenous resolution of inflammation pathways may provide a novel therapeutic strategy in cardiovascular prevention.

Highlights

The inflammatory response in atherosclerosis is characterized both by a continuous immune activation [1] and a failure in the resolution of inflammation [2]
docosahexaenoic acid (DHA) promotes the phosphorylation of p38mitogen-activated protein kinase (MAPK), alongside the activation of the peroxisome proliferator-activated receptor-γ (PPAR-γ) [70]. In line with these results, eicosapentaenoic acid (EPA) prevents the β-catenin-induced vascular smooth muscle cells (VSMCs) trans-differentiation towards osteoblast-like cells through the activation of PPAR- γ [71]. These experiments shed light on the potential pathways involved in the reduction of vascular calcification by omega-3 polyunsaturated fatty acids (PUFAs) (Fig. 3); they do not address whether these actions are mediated directly by DHA and EPA or their downstream-derived proresolving mediators, are receptor dependent, or a consequence of changes in the membrane composition
The proresolving mediators derived from omega-3 PUFAs may interact at several points of the atherosclerosis process

Summary

Introduction

The inflammatory response in atherosclerosis is characterized both by a continuous immune activation [1] and a failure in the resolution of inflammation [2]. In further support of an interplay between VSMCs and immune cells during resolution, RvD2 or MaR1 alters VSMCs collagen production only in the presence of macrophage supernatants [45], suggesting that collagen production was directly affected by omega-3 PUFAs and lipid mediators derived from immune cells This interplay between immune and structural cells appears to be reciprocal, since RvE1 decreases TNFα-induced RANTES production in VSMCs, partially through ChemR23, and reducing T cell trafficking [60]. In line with these results, EPA prevents the β-catenin-induced VSMC trans-differentiation towards osteoblast-like cells through the activation of PPAR- γ [71] These experiments shed light on the potential pathways involved in the reduction of vascular calcification by omega-3 PUFAs (Fig. 3); they do not address whether these actions are mediated directly by DHA and EPA or their downstream-derived proresolving mediators, are receptor dependent, or a consequence of changes in the membrane composition. Both RvD1 and RvD2 inhibit p65 nuclear translocation [62, 77], reducing NFκB activation and as a consequence, reducing the inflammatory environment by decreasing, for example, IL-1β, IL-6, [61], and CCL-2 expression [62] (Fig. 3)

Summary and conclusions

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