Macrophage-Specific E3 Ubiquitin Ligase TRIM31 Reduces Atherosclerotic Plaque Formation by Targeting LOX-1

BACKGROUND: Atherosclerosis is a chronic inflammatory disease marked by lipid accumulation and immune cell infiltration in arterial walls. Macrophages contribute by internalizing oxidized low-density lipoprotein, forming foam cells, and driving inflammation. The ubiquitin-proteasome system regulates immune and inflammatory responses in atherosclerosis. This study investigated the protective role of TRIM31 (tripartite motif-containing 31), an E3 ubiquitin ligase, in macrophage lipid metabolism and inflammation through selective regulation of LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1). METHODS: mice to evaluate the functional importance of Lox-1 ubiquitination in vivo (n=8 per group) and in vitro (n=5 per group). RESULTS: or K12R-variant rescue models. The TRIM31-LOX-1 axis was also confirmed by human macrophages in regulating lipid uptake and inflammation. CONCLUSIONS: TRIM31, an inducible, macrophage-enriched protective factor in atherosclerosis, restricts foam cell formation and inflammation by targeting LOX-1 for proteasomal degradation. These findings position TRIM31 as a promising therapeutic target for macrophage-driven atherogenesis.