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Updated: Feb 17, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Selective EGFR (Epidermal Growth Factor Receptor) Deletion in Myeloid Cells Limits Atherosclerosis-Brief Report
Lynda Zeboudj1, Andréas Giraud1, Lea Guyonnet1
1From the Inserm U970, Paris Cardiovascular Research Center, Université René Descartes Paris 5, France (L.Z., A.G., L.G., Y.Z., L.L., B.E., J.V., A.C., A.T., Z.M., P.-L.T., H.A.-O.); Center for Molecular Medicine of the Austrian Academy of Sciences (N.P.-M., C.J.B.) and Department of Laboratory Medicine (N.P.-M., C.J.B.), Medical University of Vienna, Austria; Division of Cardiovascular Medicine, Department of Medicine, University of Cambridge, United Kingdom (Z.M.); and Service de Réanimation Médicale, Hôpital Saint-Antoine, AP-HP, Université Pierre-et-Marie Curie, Paris (H.A.-O.).
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.
Insights
Inhibiting the epidermal growth factor receptor (EGFR) in myeloid cells significantly reduces atherosclerosis development. This inhibition limits inflammatory cytokine production and lipid uptake in macrophages, thereby reducing lesion size.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
- The role of specific signaling pathways, like EGFR, in myeloid cell function during atherosclerosis is not fully understood.
Purpose of the Study:
- To investigate the impact of epidermal growth factor receptor (EGFR) inhibition specifically within myeloid cells on the development of atherosclerosis.
Main Methods:
- Utilized chimeric mice with targeted deletion of EGFR in myeloid cells (LysMCre+Egfrlox/lox) compared to controls (LysMCre-Egfrlox/lox).
- Administered a high-fat diet and assessed atherosclerotic lesion size, macrophage accumulation, and necrotic core size over 12 weeks.
- Analyzed cytokine production (TNF-α, IL-6, IL-10, IL-12p70) by stimulated macrophages and evaluated macrophage lipid uptake and cytoskeletal rearrangements.
Main Results:
- Significant reductions in atherosclerotic lesion size were observed in mice with myeloid EGFR deletion at 4, 7, and 12 weeks.
- Reduced lesion size correlated with decreased macrophage infiltration and smaller necrotic cores.
- EGFR deletion in myeloid cells diminished TNF-α and IL-6 production but did not affect IL-10 or IL-12p70 secretion.
- Myeloid EGFR deletion impaired macrophage cytoskeletal rearrangements and reduced lipid uptake via CD36 downregulation.
Conclusions:
- Targeted deletion of EGFR in myeloid cells effectively attenuates atherosclerosis progression.
- EGFR signaling in myeloid cells promotes inflammation and lipid accumulation, contributing to atherosclerotic plaque development.
