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.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cytokines / metabolism
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Endothelium, Vascular / metabolism
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Gene Expression Regulation / drug effects*
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
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Inflammation Mediators / metabolism*
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Mitogen-Activated Protein Kinases / metabolism
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Muscle, Smooth, Vascular / metabolism
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NF-kappa B / metabolism
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Phosphatidylinositol 3-Kinases / metabolism
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Plasminogen Activator Inhibitor 1 / genetics*
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Plasminogen Activator Inhibitor 1 / metabolism
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Promoter Regions, Genetic / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Signal Transduction / drug effects*
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Vascular Diseases / drug therapy*
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Vascular Diseases / genetics
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Vascular Diseases / metabolism
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rho GTP-Binding Proteins / metabolism
Substances
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Cytokines
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Inflammation Mediators
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NF-kappa B
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Plasminogen Activator Inhibitor 1
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Phosphatidylinositol 3-Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases
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rho GTP-Binding Proteins