Abstract 583: Receptor for Advanced Glycation End Products (Ager) and Diaphanous-1 (Drf1) Suppress Macrophage Reverse Transendothelial Migration and Regression of Diabetic Atherosclerosis

Macrophages display complex trafficking properties in vivo, involving interaction with vascular endothelial cells. Macrophage migration is an important mechanism linked to the progression and regression of atherosclerosis. The underlying mechanisms involved in these processes are not fully defined. RAGE is a multiligand cell surface macromolecule, which binds distinct ligands. The RAGE cytoplasmic domain interacts with Diaphanous-1 (Drf1), both in vitro and in vivo and this interaction is essential for RAGE ligand-mediated signaling in macrophages. We tested the hypothesis that RAGE and Diaphanous-1 suppress regression of diabetic atherosclerosis; at least in part by impaired reduction of plaque macrophage content in an AGE-enriched diabetic environment. In a aorta transplantation model, we examined the morphologic changes in LDLr-/- donor plaques found in Ager-/-, Drf1-/- or WT recipient diabetic mice. After lipid normalization into Ager-/- recipient diabetic mice, we observed reduced plaque macrophage d...