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Editorial
. 2025 Oct 24;137(10):1276-1278.
doi: 10.1161/CIRCRESAHA.125.327423. Epub 2025 Oct 23.

Ensnarement of Stressed Macrophages by NETs in Atherosclerosis

Affiliations
Editorial

Ensnarement of Stressed Macrophages by NETs in Atherosclerosis

Ilana S Nazari et al. Circ Res. .
No abstract available

Keywords: Editorials; deoxyribonucleases; efferocytosis; extracellular traps; plaque, atherosclerotic.

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Conflict of interest statement

M.J. Feinstein received a consulting fee from Abbott Laboratories, NewAmsterdam Pharma, and Novo Nordisk.

Figures

Figure 1.
Figure 1.
Interactions between macrophages and NETs in atherosclerotic plaque environment. 1. ER stress (PERK-ATF4 activation) in foam cell macrophages decreases NET-induced DNase response leading to 2. accumulation of NETs in plaque environment. HMGB1 protein on NETs activates TLR4 signaling on macrophages, leading to ADAM17-mediated MERTK cleavage, 3. impairing macrophage efferocytosis of apoptotic cells and debris. 4. Impaired efferocytosis leads to higher percentage of plaque necrosis. ISRIB can inhibit the PERK-ATF4 pathway, restoring DNase response and improving NET clearance. Created in BioRender. Nazari, I. (2025) https://BioRender.com/fy3mpyy

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