The Biochemistry, Physiology and Pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo

Thromb Res. 2012 Oct;130(4):576-85. doi: 10.1016/j.thromres.2012.06.023. Epub 2012 Jul 15.


Plasminogen activator inhibitor-1 (PAI-1) is the primary physiological inhibitor of both tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA) and is consequently one the most important inhibitors of the plasminogen/plasmin system. PAI-1 attenuates fibrinolysis and increased levels of active PAI-1 have been associated with an increased risk for cardiovascular diseases. PAI-1 knock-out mice as well as PAI-1 overexpressing mice have been generated and characterized to study the role of PAI-1 in vivo. A number of PAI-1 inhibitors have been generated to study the pharmacological effect of PAI-1 inhibition in vitro and in vivo. The current review provides an overview of 1) the biochemical features of PAI-1, 2) the role of PAI-1 in diverse pathologies, 3) the in vitro and in vivo data obtained with PAI-1 inhibitors and 4) the vitronectin, glycosylation and species dependency of PAI-1 inhibition.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Drug Discovery / methods
  • Fibrinolysis
  • Gene Expression Regulation
  • Humans
  • Metabolic Diseases / drug therapy
  • Metabolic Diseases / genetics
  • Metabolic Diseases / metabolism
  • Molecular Targeted Therapy* / methods
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Plasminogen Activator Inhibitor 1 / chemistry
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Vitronectin / metabolism


  • Plasminogen Activator Inhibitor 1
  • Vitronectin