MK and Platelet P2Y12 Inhibition Responsive Genes
(A) The clinical cohort of healthy subjects (n = 70) began with a baseline visit (visit 1), randomized to either low- or high-dose ASA for 4 weeks each (visit 2), crossed over to the other ASA dose for 4 weeks (visit 3), ASA washout (visit 4), and 4 weeks of P2Y12 inhibitor exposure (visit 5). Red arrows indicate time points of blood collection. (B) Scatterplot of fold change differences comparing MKs treated with P2Y12 inhibitor and P2Y12-inhibited platelets from the clinical cohort. (C) Venn diagram and (D) heatmap of overlapping and differentially expressed genes observed in MKs and platelets (P < 0.05). Red color represents up-regulated and blue down-regulated genes. (E) Gene set enrichment analysis of hallmark pathways, comparison between P2Y12-inhibited pathways in MKs and platelets (P < 0.05). (F, G) Enrichment plots of (F) IFNα- and (G) IFNγ-response pathways in P2Y12-inhibited platelets. Relative gene positions in the ranked list of genes are indicated. P values were determined from the gene set enrichment analysis output. Abbreviations as in Figure 1.