Serpin E1/PAI-1: Small Molecules and Peptides

Serpin E1, also known as Plasminogen Activator Inhibitor-1 (PAI-1), is the primary inhibitor of urokinase-type and tissue-type plasminogen activators (uPA and tPA) which convert Plasminogen to Plasmin. The PA-Plasmin system is involved in fibrinolysis, tissue fibrosis, angiogenesis, wound healing, tumor cell invasion and metastasis, and obesity. Serpin E1 can promote clot formation, arterial re-endothelialization, and neointima formation while protecting against vascular intima thickening. It binds Vitronectin and inhibits vascular smooth muscle cell and endothelial cell adhesion, proliferation, and motility. Serpin E1 binds and induces the LRP-dependent internalization of cell surface complexes containing uPA, uPAR, and Integrin alpha V beta 3. Serpin E1 secretion is upregulated during inflammation, physical injury, and exposure to Angiotensin II.