First Author | Zeboudj L | Year | 2018 |
Journal | Arterioscler Thromb Vasc Biol | Volume | 38 |
Issue | 1 | Pages | 114-119 |
PubMed ID | 29191921 | Mgi Jnum | J:283406 |
Mgi Id | MGI:6385224 | Doi | 10.1161/ATVBAHA.117.309927 |
Citation | Zeboudj L, et al. (2018) Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells Limits Atherosclerosis-Brief Report. Arterioscler Thromb Vasc Biol 38(1):114-119 |
abstractText | 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-alpha (tumor necrosis factor-alpha) 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-alpha production, lipid uptake, and consecutively reduces atherosclerosis development. |