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Scientific article
English

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

ContributorsKruithof, Egbert
Published inThrombosis and haemostasis, vol. 100, no. 6, p. 969-975
Publication date2008
Abstract

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-kappaB 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
  • 1-Phosphatidylinositol 3-Kinase/metabolism
  • Animals
  • Cytokines/metabolism
  • Endothelium, Vascular/metabolism
  • Gene Expression Regulation/drug effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use
  • Inflammation Mediators/metabolism
  • Mitogen-Activated Protein Kinases/metabolism
  • Muscle, Smooth, Vascular/metabolism
  • NF-kappa B/metabolism
  • Plasminogen Activator Inhibitor 1/genetics/metabolism
  • Promoter Regions, Genetic/drug effects
  • Proto-Oncogene Proteins c-akt/metabolism
  • Signal Transduction/drug effects
  • Vascular Diseases/drug therapy/genetics/metabolism
  • Rho GTP-Binding Proteins/metabolism
Citation (ISO format)
KRUITHOF, Egbert. Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins. In: Thrombosis and haemostasis, 2008, vol. 100, n° 6, p. 969–975. doi: 10.1160/TH08-04-0269
Identifiers
ISSN of the journal0340-6245
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