EDN1 and brain injury: Studies have demonstrated that increased BBB leakage was associated with loss of TJ proteins and higher BBB-permeability biomarkers, including matrix metalloproteinases (MMP-9 and MMP-2), vascular endothelial growth factors (VEGFs), angiopoietin (ANG-1, ANG-2, ANG-3, and ANG-4), and endothelin-1 (ET-1), in brain injuries [12,13,14].