Atherosclerosis is usually investigated in murine models with disrupted lipid homeostasis, primarily the ApoE-/- and the LDLR-/- mouse. The impact of antigen-presenting cells (APCs) on lipid homeostasis remains unclear. In our study using a LacZ reporter mouse, we observed an enrichment of CD11c+ cells in the aortae of ApoE-/- mice. Long-term systemic depletion of Wildtype-CD11c+ cells in bone marrow transplanted ApoE-/- mice led to a significant increase in plaque formation, which correlated with decreased serum ApoE levels.
Analyzing CD11ccre+ApoEfl/fl and Albumincre+ApoEfl/fl mice, we found that approximately 70% of ApoE is liver-derived while about 25% comes from CD11c+ cells. Both strains exhibited a significantly higher burden of atherosclerotic plaques. Specific deletion of ApoE in CD11c+ cells resulted in increased inflammation, as indicated by elevated IL-1β serum levels.
Additionally, exposure to acLDL enhanced cholesterol efflux from bone marrow derived CD11c+ cells in vitro.
For the first time, our findings quantify the contribution of ApoE from CD11c+ cells and demonstrate that these cells help mitigate atherosclerosis through ApoE secretion.
