Abstract 155: MicroRNA-146a Suppression of NF-κB-driven Monocyte/Macrophage Activation and Atherosclerosis is Regulated by Cellular ApoE Expression

Apolipoprotein E (apoE) exerts anti-inflammatory properties that protect against atherosclerosis and other inflammatory diseases. However, the mechanisms by which apoE suppresses the activation of leukocytes remain incompletely understood. An assessment of apoE expression levels among major leukocyte subsets in wild-type mice revealed that only macrophages and monocytes express apoE abundantly. An absence of Apoe expression in mouse macrophages and monocytes resulted in enhanced NF-κB signaling and an exaggerated inflammatory response upon stimulation with lipopolysaccharide. This correlated with reduced levels of microRNA-146a, a critical negative regulator of NF-κB signaling. Restoration of apoE expression in Apoe-/- macrophages and monocytes enhanced miR-146a levels, while silencing apoE expression in wild-type mouse monocytes reduced miR-146a levels. Mechanistically, apoE increased the expression of transcription factor PU.1, which raised levels of pri-miR-146 transcripts, demonstrating that apoE exer...