Summary
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.
Keywords
Plasminogen activator inhibitor - apoptosis - vascular remodelling - cancer