Historical analysis of PAI-1 from its discovery to its potential role in cell motility and disease.

Department of Cellular Biology, Division of Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.

Although plasminogen activator inhibitor 1 (PAI-1) is one of the primary regulators of the fibrinolytic system, it also has dramatic effects on cell adhesion, detachment and migration. PAI-1 also differs from other serine protease inhibitors (serpins) in that it is a trace protein in plasma, it has a short half-life in vivo, its synthesis is highly regulated, and it binds to the adhesive glycoprotein vitronectin (VN) with high affinity and specificity. These unique and diverse properties of PAI-1 probably account for the many observations in the literature that correlate abnormalities in PAI-1 gene expression with a variety of pathological conditions. In this review, we discuss the discovery, origin, properties and regulation of PAI-1, and then speculate about its potential role in vascular disease, fibrosis, obesity and the metabolic syndrome, and cancer.

PMID: 15841306 [PubMed - indexed for MEDLINE]