A Collagen-Derived Oligopeptide from Salmo salar Collagen Hydrolysates Restrains Atherogenesis in ApoE-/- Mice via Targeting P2Y12 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 P2Y12 receptors to regulate G beta gamma i-PI3K-Akt signaling and G alpha i-cAMP-VASP signaling is demonstrated. The molecular docking results also reveal a strong binding energy with the P2Y12 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.

Automated summary

This study demonstrated that collagen hydrolysates containing OG peptides have antiplatelet and anti-atherosclerotic activities. Peptide OG-5 inhibits platelet aggregation and tail thrombosis formation by targeting P2Y12 receptors and regulating signaling pathways. It also inhibits the release of inflammatory cytokines and migration of vascular smooth muscle cells. These findings suggest that collagen hydrolysates with OG peptides could be developed as a dietary supplement to prevent atherogenesis and thrombotic disease.