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: Transcriptomic profiling, macrophage-specific Trim31 knockout ( Trim31 fl/fl Lyz2 cre ) and overexpression ( Trim31 Lyz2-KI ) mice, and Lox-1 knockout ( Lox-1 −/− ) models were used to examine the impact of TRIM31 in vivo (n=8 per group). TRIM31 substrates were identified using single-cell RNA sequencing…