Protective effects of oligomeric bioactive peptides against atherosclerosis in an atherogenic diet-induced mouse model

This study investigated the anti-atherosclerotic potential of two blue mussel-derived bioactive peptides, PIISVYWK (P1) and FSVVPSPK (P2), using an atherogenic diet (AD)-induced mouse model. Administration of both peptides significantly attenuated atherosclerotic lesion development and markedly improved serum lipid profiles, as evidenced by reductions in low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TG) levels, along with an increase in high-density lipoprotein (HDL) concentrations. Mechanistic investigations revealed that P1 and P2 upregulated ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1) expression, consistent with enhanced cholesterol efflux while downregulating of cluster of differentiation 36 (CD36) and scavenger receptor class A1 (SR-A1) suggesting reduced cholesterol uptake. Furthermore, both peptides were associated with reduced lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) expression and increased endothelial nitric oxide synthase (eNOS) expression which is responsible for endothelial protection. The peptides also reduced intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) consistent with attenuated vascular inflammation. In addition, treatment with P1 and P2 improved hepatic function, as demonstrated by reduced serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Collectively, these findings highlight the therapeutic potential of P1 and P2 as promising bioactive agents for the prevention and management of atherosclerosis.