title: Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia?
abstract: Pre-eclampsia (P-Ec) is a complex multisystem disorder of unknown aetiology reported to occur in about 6% to 8% of all pregnancies throughout the world. This disease is associated with fibrin deposition and occlusive lesions in placental vessels. Pro-thrombin activatable fibrinolysis inhibitor (pro-TAFI) is a relatively recently described glycoprotein that can be converted into its active form (TAFIa) by thrombin, thrombin-thrombomodulin and plasmin. TAFIa potentially inhibits fibrinolysis by removing C-terminal lysine and arginine residues from fibrin. These residues are required for adsorption of tissue-type plasminogen activator (t-PA) and plasminogen to fibrin. Therefore, TAFIa decreases plasmin formation and protects the fibrin clot against lysis. An increased of pro-TAFI/TAFIa levels has been reported in some clinical conditions associated with thrombotic tendency, as type II diabetes mellitus, deep vein thrombosis and symptomatic artery disease. Few studies have investigated pro-TAFI/TAFIa in normal or complicated pregnancy but contrasting results were reported. Understanding the role of pro-TAFI/TAFIa in the pathogenesis of P-Ec can hold great promise for improving P-Ec management. In this context, a large-scale study evaluating plasma TAFI antigen and activity, its synthesis and metabolism in pre-eclamptic women is required. Recently new selective TAFIa inhibitors have been developed. The design of a new therapy to treat and/or prevent P-Ec, based on successful use of TAFIa inhibitors, may have significant clinical ramifications.
authors.affiliation: Faculty of Pharmacy, Federal University of Minas Gerais, Brazil, and Department of Urology, Southampton University Hospitals NHS Trust, UK. lucim@farmacia.ufmg.br
authors.forename: Luci Maria SantAna
authors.initials: LM
authors.lastname: Dusse
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Cooper
authors.forename: Bashir A
authors.initials: BA
authors.lastname: Lwaleed
mesh_terms: D025901:Carboxypeptidase B2 / Q000097:blood / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy; D011486:Protein C / Q000378:metabolism; D011498:Protein Precursors / Q000096:biosynthesis; D013917:Thrombin / Q000502:physiology; D018180:Thrombomodulin / Q000502:physiology
chemical_list: D011486:Protein C; D011498:Protein Precursors; D018180:Thrombomodulin; D025901:Carboxypeptidase B2; D013917:Thrombin