Metrnl Reduces Thrombosis and Acute Myocardial Injury Through Inhibition of Platelet Activation via CD36 Receptor Degradation
Authors' conclusion
We identify Metrnl in both endogenous secretion and exogenous administration as a novel inhibitor of platelet activation and thrombus formation without causing bleeding risk. Metrnl is a novel ligand for the CD36 receptor, which has a specific Metrnl binding domain. Metrnl inhibits platelet activation by promoting CD36 degradation via acetylation at lysine 403 of CD36.
Study context
- Population
- Human and rodent platelets; global and platelet-specific Metrnl knockout mice
Main finding
As reported in the abstract
- Metrnl deficiency potentiated thrombosis via platelet activation rather than coagulation or fibrinolysis
- Exogenous Metrnl directly inhibited platelet activation and thrombosis without bleeding risk, alone or with clopidogrel
- Platelet Metrnl inhibited platelet activation and thrombosis in a secretory manner
- CD36 identified as platelet receptor for Metrnl; Metrnl induced CD36 degradation via domain aa 280-439 and acetylation at lysine 403, decreasing SRC-ERK5 signalling
- Metrnl mitigated microvascular thrombosis and acute myocardial ischemia/reperfusion injury in mice
Safety
- No bleeding risk with Metrnl alone or combined with clopidogrel
Original publication
Metrnl Reduces Thrombosis and Acute Myocardial Injury Through Inhibition of Platelet Activation via CD36 Receptor Degradation. Circulation. Published 18 August 2026. doi:10.
Summarised from the published abstract; every number is checked against it