2025/10/14 by Fei Fang, Erxiang Wang, Hanqiao Yang +5 · 1 voice
Immunology and Microbiology · #Immune cells in cancer #Immune responses and vaccinations #Phagocytosis and Immune Regulation
paper · pdf · doi:10.1038/s41467-025-64201-8
openalex created_date 2025/10/14 · openalex publication_date 2025/10/14 · openalex updated_date 2026/07/28
Disruption in the dynamic stability of macrophage pro/anti-inflammatory phenotypes within plaques significantly impacts chronic vascular inflammation and exacerbates atherosclerosis. Reprogramming macrophages from pro-inflammatory to anti-inflammatory phenotype mitigates atherosclerosis progression. However, chronic inflammatory stimulation induces a closed chromatin state in atherosclerotic macrophages, inhibiting their phenotype reprogramming. This study demonstrates that restoring mitochondrial respiration increases histone acetylation (AcH3) and enhances chromatin accessibility in atherosclerotic macrophages, restarting macrophage phenotype reprogramming. Additionally, we identified that miR-10a can facilitate mitochondrial respiration and reorganize macrophage reprogramming. To optimize delivery, prolong circulation time, and target pro-inflammatory macrophages, we developed red blood cell membrane-modified liposome nanoparticles (miR-10a@H-MNP) to deliver miR-10a. Hyaluronic acid was conjugated to the liposomes to specifically target pro-inflammatory macrophages in plaque. Intravenous administration of miR-10a@H-MNP significantly alleviated atherosclerosis progression in male mice. Thus, the epigenomic priming approach developed here effectively triggers macrophage reprogramming in atherosclerosis, presenting a promising metabolically based epigenetic modulation method for plaque clearance. This study shows that restoring mitochondrial respiration in atherosclerotic macrophages reopens their chromatin, enabling phenotype reprogramming. Using targeted liposomes to deliver miR-10a, researchers successfully reduced atherosclerosis in mice by reprogramming macrophage phenotypes. The findings offer a promising epigenetic therapy for atherosclerosis