Pathological stimuli reduce eNOS expression and NO bioavailability while upregulating hypoxia-inducible factor-1 (HIF-1), endothelin-1 (ET-1), and plasminogen activator inhibitor-1 (PAI-1), collectively exacerbating endothelial dysfunction, enhancing thrombogenicity, and promoting vascular smooth muscle proliferation (37). Here, SERPINE1 is linked to endothelial dysfunction.