The effect of plasminogen activator inhibitor type 1 on apoptosis

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH08-04-0234
Issue:2008: 100/6 (Dec) pp. 955-1217
Pages:1037-1040

The effect of plasminogen activator inhibitor type 1 on apoptosis

David J. Schneider1; Yabing Chen2; Burton E. Sobel1

1Department of Medicine and the Cardiovascular Research Institute, University of Vermont, Burlington, Vermont, USA; 2Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA

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

cancer, plasminogen activator inhibitor, apoptosis, vascular remodelling

DOI

http://dx.doi.org/10.1160/TH08-04-0234

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