A Narrative Review on Plasminogen Activator Inhibitor-1 and Its (Patho)Physiological Role: To Target or Not to Target?

Int J Mol Sci. 2021 Mar 8;22(5):2721. doi: 10.3390/ijms22052721.

Abstract

Plasminogen activator inhibitor-1 (PAI-1) is the main physiological inhibitor of plasminogen activators (PAs) and is therefore an important inhibitor of the plasminogen/plasmin system. Being the fast-acting inhibitor of tissue-type PA (tPA), PAI-1 primarily attenuates fibrinolysis. Through inhibition of urokinase-type PA (uPA) and interaction with biological ligands such as vitronectin and cell-surface receptors, the function of PAI-1 extends to pericellular proteolysis, tissue remodeling and other processes including cell migration. This review aims at providing a general overview of the properties of PAI-1 and the role it plays in many biological processes and touches upon the possible use of PAI-1 inhibitors as therapeutics.

Keywords: PAI-1; aging; cancer; cardiovascular disease; fibrinolysis; fibrosis; inflammation; plasminogen activator inhibitor-1.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / immunology
  • Cardiovascular Diseases* / metabolism
  • Cardiovascular Diseases* / pathology
  • Cell Movement / immunology*
  • Fibrinolysis / immunology*
  • Fibrosis
  • Humans
  • Neoplasm Proteins* / antagonists & inhibitors
  • Neoplasm Proteins* / immunology
  • Neoplasm Proteins* / metabolism
  • Neoplasms* / drug therapy
  • Neoplasms* / immunology
  • Neoplasms* / pathology
  • Plasminogen Activator Inhibitor 1* / immunology
  • Plasminogen Activator Inhibitor 1* / metabolism
  • Proteolysis*
  • Urokinase-Type Plasminogen Activator / immunology
  • Urokinase-Type Plasminogen Activator / metabolism

Substances

  • Neoplasm Proteins
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • Urokinase-Type Plasminogen Activator