Rice bran peptides target lectin-like oxidized low-density lipoprotein receptor-1 to ameliorate atherosclerosis

Food-derived multifunctional peptides offer numerous health benefits through different biochemical pathways. However, their impact on aging-related atherosclerotic cardiovascular disease (ASCVD), especially atherosclerosis, remains underexplored despite cardiovascular disease (CVD) being the leading cause of death globally. In this study, NHANES data and Mendelian randomization were used to analyze the association between lipid metabolism disorders, systemic immune responses, dietary inflammatory index, and ASCVD. The results showed that they were all positively correlated with ASCVD. A dietary intervention was used to induce a mouse model of atherosclerosis through a high-fat diet (HFD). Our findings demonstrate that rice bran peptide could mitigate the typical pathological features of atherosclerosis. Molecular docking analysis further predicted that lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a key target of rice bran peptide. This prediction was validated through a two-cell model of endothelial cells and lox-1-interfered macrophages. Therefore, targeting LOX-1 with rice bran peptide inhibits the excessive uptake of oxidized LDL (ox-LDL) by macrophages, thereby hindering the mass production of foam cells, which is crucial in preventing the early onset of atherosclerosis.