Thrombin activatable fibrinolysis inhibitor (TAFI): a role in pre-eclampsia?
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.
Dusse
Luci Maria SantAna
LM
Faculty of Pharmacy, Federal University of Minas Gerais, Brazil, and Department of Urology, Southampton University Hospitals NHS Trust, UK. lucim@farmacia.ufmg.br
Cooper
Alan J
AJ
Lwaleed
Bashir A
BA
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
D011486:Protein C; D011498:Protein Precursors; D018180:Thrombomodulin; D025901:Carboxypeptidase B2; D013917:Thrombin