To determine the consequences of specific inhibition of EGFR (epidermal growth factor receptor) in myeloid cells in atherosclerosis development.Approach and Results—
Atherosclerotic lesion size was significantly reduced in irradiated Ldlr−/− mice reconstituted with LysMCre+Egfrlox/lox bone marrow, compared with chimeric Ldlr−/− mice reconstituted with LysMCre−Egfrlox/lox bone marrow, after 4 (−43%; P<0.05), 7 (−34%; P<0.05), and 12 weeks (−54%; P<0.001) of high-fat diet. Reduction of lesion size was associated with marked reduction in macrophage accumulation and necrotic core size. Specific deletion of Egfr in myeloid cells reduced TNF-α (tumor necrosis factor-α) and IL (interleukin)-6 production by stimulated macrophages but had no effect on IL-10 and IL-12p70 secretion. Finally, we found that myeloid deletion of Egfr limited cytoskeletal rearrangements and also lipid uptake by macrophages through a downregulation of the scavenger receptor CD36 (cluster of differentiation 36).Conclusions—
Gene deletion of Egfr in myeloid cells limits IL-6 and TNF-α production, lipid uptake, and consecutively reduces atherosclerosis development.