Once activated, endothelial cells secrete endothelin-1 (ET-1), von Willebrand factor (vWF), nitric oxide, and endothelial nitric oxide synthase, resulting in unstable vascular tone, with decreased vasodilation and increased vasoconstriction causing ischemia and tissue hypoxia [119,120,121,122,123,124]. Here, EDN1 is linked to ischemia.