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

Accepted version
Peer-reviewed

Type

Article

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Authors

Zeboudj, Lynda 
Giraud, Andréas 
Guyonnet, Lea 
Zhang, Yujiao 
Laurans, Ludivine 

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 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.

Description

Keywords

atherosclerosis, foam cells, inflammation, macrophages, mice, Animals, Atherosclerosis, Bone Marrow Transplantation, CD36 Antigens, Cytoskeleton, Diet, High-Fat, Disease Models, Animal, ErbB Receptors, Gene Deletion, Interleukin-6, Macrophages, Male, Mice, Knockout, Necrosis, Plaque, Atherosclerotic, Receptors, LDL, Tumor Necrosis Factor-alpha, Whole-Body Irradiation

Journal Title

Arterioscler Thromb Vasc Biol

Conference Name

Journal ISSN

1079-5642
1524-4636

Volume Title

38

Publisher

Ovid Technologies (Wolters Kluwer Health)
Sponsorship
British Heart Foundation (RG/15/11/31593)