Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells Limits Atherosclerosis
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 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.
- Received July 7, 2017.
- Accepted November 17, 2017.
- © 2017 American Heart Association, Inc.