Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 38, Issue 1, Pages 114-119Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.117.309927
Keywords
atherosclerosis; foam cells; inflammation; macrophages; mice
Categories
Funding
- Institut National de la Sante et de la Recherche Medicale
- British Heart Foundation
Ask authors/readers for more resources
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- (tumor necrosis factor-) 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- production, lipid uptake, and consecutively reduces atherosclerosis development.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available