Inhibition of atherosclerotic plaque calcification by Omega-3 polyunsaturated fatty acids through the resolvin E1 receptor ChemR23.

Background: The immune cell response in atherosclerotic plaques is characterized by an impaired resolution of inflammation (1). Resolvin E1 (RvE1), a specialized pro-resolving lipid mediator derived from omega-3 polyunsaturated fatty acids (PUFA) has been shown to play a critical role in atherosclerosis by promoting the resolution of the inflammation (2). The aim of the present study was to unravel the role of omega-3 PUFA, RvE1 and the RvE1 receptor ChemR23 in the process of atherosclerotic plaque calcification. Methods: Fat-1 transgene (Fat-1tg), which enables the endogenous production of n-3 PUFA, was inserted in apolipoprotein E (ApoE)-deficient mice, in combination or not with genetic deletion of ChemR23. Calcification was assessed by Alizarin Red staining and macrophage markers were assessed by immunohistochemistry in aortic root sections. Results: Our results show that 72 week old Fat-1tg × Apoe^-/- mice developed less atherosclerotic plaque calcification compared with Apoe^-/- mice (0-3% vs 4-8%, p < 0.001). Moreover, deletion of ChemR23 enhanced atherosclerotic plaque calcification (4-13% vs. 4-8%, p < 0.001), and this effect was not reversed by the presence of Fat-1tg (4-14% vs. 4-8%, p < 0.001). Furthermore, the Fat- 1tg × Apoe^-/- mice had significantly higher expression of the M2 macrophage marker Arg1 compared with Apoe^-/- mice (17.4 ± 2.5% vs 5.1 ± 1.5%; p < 0.0001), which was reversed by genetic deletion of ChemR23 (5.0 ± 1.1% vs. 17.4 ± 2.5%; p < 0.0001 vs Fat-1tg × Apoe^-/- mice). Conclusion: These results suggest that the beneficial effects of Fat- 1tg were mediated through ChemR23. Hence, omega-3 PUFA may have a therapeutic potential for reducing atherosclerotic plaque calcification through RvE1-signaling by means of ChemR23. [ABSTRACT FROM AUTHOR]