Furthermore, the enrichment of endothelial dysfunction (vascular endothelial growth factor receptor-2, heme oxygenase 1); immune dysregulation (CD40L, interleukin-10, and C-type lectin domain family 5 member A); and coagulation-related markers (plasminogen activator inhibitor-1 and circulating free DNA) in severe sepsis and septic shock underscores key pathways driving disease escalation (Figure 7D). This evidence concerns the gene SERPINE1 and endothelial dysfunction.