Mechanism of tilapia skin antioxidant pentapeptide on atherosclerosis: Inhibition of angiogenesis and oxidative stress

Atherosclerosis (AS), the pathological core of cardiovascular disease, features endothelial dysfunction, inflammation, oxidative stress, and angiogenesis-driven plaque instability. This study investigates the therapeutic potential of tilapia skin-derived pentapeptide Leu-Ser-Gly-Tyr-Gly (LYG) against AS by targeting angiogenesis and oxidative stress. The results show LYG is a structurally stable antioxidant peptide. LYG down-regulates key angiogenic factors, thereby inhibiting angiogenesis. It also activates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway to reduce oxidative stress and reduces the expression of oxidized low-density lipoprotein receptor (LOX-1) and angiotensin II type 1 receptor (AT1), thereby improving endothelial function. Furthermore, LYG suppresses the expression and release of both ox-LDL- and LPS-induced inflammatory mediators and adhesion molecules, thereby mitigating atherosclerotic cardiovascular disease (ASCVD). This study elucidates the potential of tilapia skin-derived peptide LYG against AS by inhibiting angiogenesis and protecting endothelial cells, while also offering new insights into high-value utilization of tilapia processing by-products. • Tilapia pentapeptide Leu-Ser-Gly-Tyr-Gly (LYG) inhibits atherosclerotic cardiovascular disease. • HOMO-LUMO analyses and quantum chemical calculations were performed on LYG. • Active site and stability analysis of LYG.