Abstract
The authors investigated the impact of antiplatelet therapy on the megakaryocyte (MK) and platelet transcriptome. RNA-sequencing was performed on MKs treated with aspirin or P2Y12 inhibitor, platelets from healthy volunteers receiving aspirin or P2Y12 inhibition, and platelets from patients with systemic lupus erythematosus (SLE). P2Y12 inhibition reduced gene expression and inflammatory pathways in MKs and platelets. In SLE, the interferon (IFN) pathway was elevated. In vitro experiments demonstrated the role of P2Y12 inhibition in reducing IFNα-induced platelet-leukocyte interactions and IFN signaling pathways. These results suggest that P2Y12 inhibition may have therapeutic potential for proinflammatory and autoimmune conditions like SLE.