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/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|
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|Research group||Endothélium vasculaire (11)|
|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|