A Collagen-Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE-/- Mice via Targeting P2 Y12 Receptor

Scope: Collagen hydrolysates have been reported with a variety of biological activities. The previous study has separated and identified a series of Hyp-Gly containing antiplatelet Peptides from collagen hydrolysates from Salmo salar. But the target and underlying mechanism in platelets remains unknown.

Methods and results: In this study, peptide OGEFG (OG-5) inhibits platelet aggregation especially induced by 2MeS-ADP and attenuates tail thrombosis formation by 30% in a dose-dependent manner, via apparent antagonism effects on P₂ Y₁₂ receptors to regulate Gβγi-PI3K-Akt signaling and Gαi-cAMP-VASP signaling is demonstrated. The molecular docking results also reveal a strong binding energy with the P₂ Y₁₂ receptor of peptide OG-5 (-10.70 kcal mol^-1 ). In vitro study suggests that OG-5 inhibited the release of inflammatory cytokines in endothelial cells and macrophage cells, migration of vascular smooth muscle cell induced by ADP, which is highly released in ApoE^-/- mice. Long-term administration of OG-5 significantly reduces atherosclerotic plaque formation without side effects in ApoE^-/- mice, exhibiting a comparable effect with aspirin.

Conclusion: These results reveal that collagen hydrolysates with OG-containing Peptides have potential to be developed as an effective diet supplement to prevent the occurrence of atherogenesis and thrombotic disease.