Abstract 134: Myeloid Disabled Homolog 2 (Dab2) Controls Liver Inflammation and Atherosclerosis

Inflammatory (M1) macrophages contribute to the pathogenesis of atherosclerosis, but the intracellular mediators of macrophage polarization are not fully understood. We identified the adaptor protein disabled homolog 2 (Dab2) as a novel regulator of phenotypic switching in macrophages. Dab2 expression is upregulated in M2 and suppressed in M1 macrophages. Dab2 in macrophages dampens NF-κB signaling by binding to TRAF6. Genetic deletion of Dab2 predisposes macrophages to adopt a proinflammatory M1 phenotype, and mice with myeloid cell-specific deletion of Dab2 (Dab2fl/flLysMCre mice) show increased inflammation upon challenge with lipopolysaccharide. To test the role of myeloid Dab2 in the pathogenesis of atherosclerosis we performed a bone marrow transplant of WT and Dab2 null bone marrow into LDLR-/- mice followed by western diet feeding for 9 or 20 weeks. Surprisingly, after 20 weeks of western diet feeding, Dab2-null chimeric mice had decreased lesion area by en face analysis of aortic arches and a tre...