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

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH08-04-0269
Issue:2008: 100/6 (Dec) pp. 955-1217
Pages:969-975

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

Egbert K. O. Kruithof

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

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

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

DOI

http://dx.doi.org/10.1160/TH08-04-0269

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