Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells Limits Atherosclerosis - Brief Report

Abstract

Objective - 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 LysM Cre+ Egfr lox/lox bone marrow, compared with chimeric Ldlr -/- mice reconstituted with LysM Cre- Egfr lox/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.