TREM2 encodes plaque macrophage plasticity to mediate atherosclerosis regression

TREM2 expression on plaque macrophages, not newly recruited monocytes, is required for atherosclerosis regression in mice, with deletion impairing necrotic core resolution.

• Why it matters: Cholesterol lowering stabilizes plaques, but the molecular control of plaque remodeling and regression is unclear, limiting targeted strategies to promote beneficial resolution.
• What they did: The study used macrophage- or monocyte-specific Trem2 deletion during regression in mice, then tested efferocytosis using an in vitro Ex-LAM model after lipid unloading.
• The result: Prior lipid priming enhanced efferocytosis and gene programs in Ex-LAMs, while augmented TREM2 signaling via genetic models or agonist treatment accelerated efferocytosis in vitro and plaque regression in vivo.

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