AI Article Synopsis
- The study investigates the effects of inhibiting EGFR in myeloid cells on the development of atherosclerosis.
- Results showed that irradiated mice with specific bone marrow reconstitution had significantly smaller atherosclerotic lesions after a high-fat diet, indicating less macrophage accumulation and necrotic core size.
- The deletion of EGFR in these cells led to reduced production of pro-inflammatory cytokines TNF-α and IL-6, less lipid uptake by macrophages, and ultimately a decrease in atherosclerosis progression.
Article 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 mice reconstituted with bone marrow, compared with chimeric mice reconstituted with bone marrow, after 4 (-43%; <0.05), 7 (-34%; <0.05), and 12 weeks (-54%; <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 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 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 in myeloid cells limits IL-6 and TNF-α production, lipid uptake, and consecutively reduces atherosclerosis development.
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| http://dx.doi.org/10.1161/ATVBAHA.117.309927 | DOI Listing |
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