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Plasminogen activator inhibitor type 1 (PAI-1) is the main physiologic inhibitor of fibrinolysis. However, it is also involved in many physiological processes such as extracellular matrix (ECM) proteolysis and remodeling, cell adhesion, motility, and apoptosis, angiogenesis, etc. The aim of the study was to summarize current knowledge and gain insights into the mechanisms of PAI-1 action in the processes of stromal remodeling and diseases with considerable matrix pathologies (atherosclerosis, tissue fibrosis, cancer metastasis, pregnancy related complications, etc). As a component of an early cellular response to injury, PAI-1 reacts with membrane surface proteins and participates in the initiation of intracellular signaling, specifically cytoskeletal reorganization and motility. Complexity of ECM homeostasis resides in varying relation of the plasminogen system components and other matrix constituents. Inflammatory mediators (transforming growth factor-β and interferon-γ) and hormones (angiotensin II) are in the close interdependent relation with PAI-1. Also, special attention is devoted to the role of increased PAI-1 concentrations due to the common 4G/5G polymorphism. Some of the novel mechanisms of ECM modification consider PAI-1 dependent stabilization of urokinase mediated cell adhesion, control of the vascular endothelial cadherin trafficking and interaction with endothelial cells proteasome, its relation to matrix metalloproteinase 2 and osteopontin, and oxidative inhibition by myeloperoxidase. Targeting and/or alteration of PAI-1 functions might bring benefit to the future therapeutic approaches in diseases where ECM undergoes substantial remodeling.

The plasminogen activator inhibitor type 1 (PAI-1) is the main inhibitor of tissue plasminogen activator and urokinase type plasminogen activator in the blood. Besides the key regulatory role in fibrinolysis, plasmin and its activators and inhibitors are responsible for the processes of extracellular matrix turnover and remodeling, cellular adhesion and migration, thus they participate in many pathophysiological processes such as thrombosis, fibrosis, atherosclerosis, cancer spread, and other. The measurement of PAI-1 expression and its levels is suggested for a risk factor assessment in certain diseases. Also, PAI-1 is being considered a potential therapeutic target that could modify disease development and progression. The aim of this work is to outline significant findings regarding PAI-1 application in diagnostics, risk factor assessment, and pathogenetic treatment of different diseases.