A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to
Machteld Sillen1, Paul J Declerck1
1Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, B-3000 Leuven, Belgium.
International Journal of Molecular Sciences
|April 3, 2021
Summary
Plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the plasminogen system, primarily inhibiting fibrinolysis. PAI-1 also influences cell migration and tissue remodeling, with potential therapeutic applications for PAI-1 inhibitors.
Area of Science:
- Biochemistry
- Molecular Biology
- Physiology
Background:
- Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of plasminogen activators (PAs).
- PAI-1 plays a crucial role in regulating the plasminogen/plasmin system, impacting processes like fibrinolysis.
Purpose of the Study:
- To provide a comprehensive overview of PAI-1 properties.
- To elucidate the diverse biological roles of PAI-1.
- To explore the therapeutic potential of PAI-1 inhibitors.
Main Methods:
- Literature review of PAI-1 properties and functions.
- Analysis of PAI-1's inhibitory mechanisms on tissue-type PA (tPA) and urokinase-type PA (uPA).
- Examination of PAI-1 interactions with ligands like vitronectin and cell receptors.
Main Results:
- PAI-1 is a fast-acting inhibitor, mainly attenuating fibrinolysis by inhibiting tPA.
- PAI-1's functions extend beyond fibrinolysis, including pericellular proteolysis, tissue remodeling, and cell migration via uPA inhibition and ligand interactions.
- PAI-1's multifaceted roles highlight its significance in various biological pathways.
Conclusions:
- PAI-1 is a critical regulator with broad physiological functions.
- Understanding PAI-1's mechanisms is essential for comprehending its role in health and disease.
- PAI-1 inhibitors represent a promising therapeutic avenue for conditions involving dysregulated plasminogen system activity.
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