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

Published in Thrombosis and haemostasis. 2008, vol. 100, no. 6, p. 969-75
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/metabolismAnimalsCytokines/metabolismEndothelium, Vascular/metabolismGene Expression Regulation/drug effectsHumansHydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic useInflammation Mediators/metabolismMitogen-Activated Protein Kinases/metabolismMuscle, Smooth, Vascular/metabolismNF-kappa B/metabolismPlasminogen Activator Inhibitor 1/genetics/metabolismPromoter Regions, Genetic/drug effectsProto-Oncogene Proteins c-akt/metabolismSignal Transduction/drug effectsVascular Diseases/drug therapy/genetics/metabolismRho GTP-Binding Proteins/metabolism
PMID: 19132219
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Research group Endothélium vasculaire (11)
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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. 969-75. doi: 10.1160/TH08-04-0269 https://archive-ouverte.unige.ch/unige:2533

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Deposited on : 2009-08-28

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