Inhibiting the P2Y12 Receptor in Megakaryocytes and Platelets Suppresses Interferon-Associated Responses
Megakaryocytes (MKs) and platelets are recognized mediators of inflammation and altered immunity. While antiplatelet therapies are widely used to prevent cardiovascular events, their role in attenuating platelet-mediated inflammation is uncertain. This study was designed to investigate the transcriptomic effect of APT on MKs and its impact on proinflammatory pathways. We demonstrated a significant effect on the MK transcriptome following P2Y12 receptor inhibition. Specifically, we found a significant downregulation of IFN pathways with P2Y12 receptor inhibition. In conclusion, targeting the P2Y12 receptor modulates MK and platelet inflammatory signaling pathways. P2Y12-mediated suppression of MK IFNa signaling may benefit proinflammatory diseases Overall design: We used human CD34+-derived MKs from 4 donors that were treated with aspirin, P2Y12 inhibition or both together for 24 hours and performed RNA-seq.