Plasminogen Activator Inhibitor Protease Domain Drives Venous Fibrosis

Plasminogen activator inhibitor-1 (PAI-1) is a multifunctional enzyme that inhibits fibrinolysis and modulates tissue fibrosis. Two domains of PAI-1 drive these processes: an antiprotease (P) domain that inhibits plasmin generation and consequently matrix metalloprotease (MMP) activation, and a vitronectin (V) binding domain that interferes with inflammatory cell adhesion. To determine the relative importance of each PAI-1 domain in venous fibrosis, we induced venous thrombosis in CRISPR-Cas9 genetically modified mice with point mutations in each respective domain (V+P−, V-P+), as well as globally gene deleted (V−P−) and wild-type (WT) mice.