Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins

Egbert K. O. Kruithof

doi:10.1160/TH08-04-0269

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2008; 100(06): 969-975
DOI: 10.1160/TH08-04-0269

Theme Issue Article

Schattauer GmbH

Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins

Egbert K. O. Kruithof

¹Division of Angiology and Hemostasis, University Hospital, Geneva, Switzerland

› Author Affiliations

Abstract

Summary

Elevated plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1), also named serpin E1, are encountered in patients with thrombophilia, atherosclerosis, septicemia and the metabolic syndrome and may be associated with an increased risk of complications. Expression of PAI-1 is increased by inflammatory stimuli and decreased by statins, drugs widely used in patients with cardiovascular disease. Increased expression of PAI-1 by inflammatory stimuli is mediated by a large variety of signal transduction pathways, which include the NF-κB and MAP kinase pathways. The downregulating effect of statins on PAI-1 expression is dependent on the inhibition of Rho family proteins and may involve an activation of PI-3 kinase/Akt signaling pathways. In this review we summarize the findings on the effect of inflammation and statins on PAI-1 expression.

Keywords

Plasminogen activator inhibitor type 1 - gene regulation - inflammation - statins

Full Text

References

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