The effect of plasminogen activator inhibitor type 1 on apoptosis

Thromb Haemost. 2008 Dec;100(6):1037-40.

Abstract

Plasminogen activator inhibitor type-1 (PAI-1), an inhibitor of plasminogen activators, inhibits formation of plasmin and plasmin-mediated proteolysis. Apoptosis, or programmed cell death, is a potentially important phenomenon in mediating overall cell death. This review focuses on the influence of PAI-1 on apoptosis. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. Mechanisms by which PAI-1 may render a cell resistant to apoptosis include its ability to inhibit generation of plasmin, its ability to inhibit caspase 3, and its ability to inhibit cell adhesion mediated by vitronectin. Inhibition of caspase 3 by PAI-1 may divert intracellular signalling from induction of apoptosis to induction of proliferation.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism
  • Apoptosis*
  • Cell Adhesion
  • Cell Proliferation
  • Cell Survival
  • Endothelium, Vascular / metabolism
  • Endothelium, Vascular / pathology
  • Humans
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Plasminogen Activator Inhibitor 1 / metabolism*
  • Signal Transduction*

Substances

  • Apoptosis Regulatory Proteins
  • Plasminogen Activator Inhibitor 1