179 - Dietary Selenomethionine Supplementation Limits Extracellular Trap Formation and Reduces Lesion Burden in a Mouse Model of Atherosclerosis

Abstract

Atherosclerosis is a chronic inflammatory disease of the vasculature characterised by the infiltration of activated neutrophils and macrophages at sites of damage within the vessel wall, which contributes to lesion formation and plaque progression. This is in part due to the formation of extracellular traps (ETs) by these invading immune cells, with inhibition of ET formation previously shown to reduce lesion formation. Selenomethionine (SeMet) is the organic form of selenium (Se), an essential trace element that functions in the regulation of the immune response. The aim of this study was to evaluate the effect of dietary SeMet supplementation within normal chow and high fat diet (HFD) fed apolipoprotein E deficient (apoE-/-) mice, as a model of atherosclerosis. Dietary supplementation with 2 mg/kg SeMet (w/w) over 12 weeks resulted in the significant reduction of atherosclerotic plaque formation in aortas from mice fed SeMet compared to controls in both the normal (0.40% vs 1.26%) and HFD (4.70% vs 6.21%) fed cohorts, as assessed by Oil Red O staining of lipid content. Isolation of bone marrow derived cells from the mice and subsequent ex vivo induction of ET formation through stimulation with phorbol 12-myristate 13-acetate (PMA) resulted in markedly less ET formation within the SeMet supplementated cohorts compared to controls as assessed through SYTOX Green staining of extracellular DNA and qPCR analysis of mitochondrial and nuclear genomic DNA within culture supernatants. Together, these data support a novel role for SeMet to mitigate ET formation and reduce atherosclerotic lesion development and highlight the potential beneficial effect of SeMet supplementation as a therapeutic strategy for atherosclerosis.