Functional stability of plasminogen activator inhibitor-1.
Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of plasminogen activators, such as tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA), and a major regulator of the fibrinolytic system. PAI-1 plays a pivotal role in acute thrombotic events such as deep vein thrombosis (DVT) and myocardial infarction (MI). The biological effects of PAI-1 extend far beyond thrombosis including its critical role in fibrotic disorders, atherosclerosis, renal and pulmonary fibrosis, type-2 diabetes, and cancer. The conversion of PAI-1 from the active to the latent conformation appears to be unique among serpins in that it occurs spontaneously at a relatively rapid rate. Latency transition is believed to represent a regulatory mechanism, reducing the risk of thrombosis from a prolonged antifibrinolytic action of PAI-1. Thus, relying solely on plasma concentrations of PAI-1 without assessing its function may be misleading in interpreting the role of PAI-1 in many complex diseases. Environmental conditions, interaction with other proteins, mutations, and glycosylation are the main factors that have a significant impact on the stability of the PAI-1 structure. This review provides an overview on the current knowledge on PAI-1 especially importance of PAI-1 level and stability and highlights the potential use of PAI-1 inhibitors for treating cardiovascular disease.
Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey.
Songul
0000-0001-8875-3637
S
Yasar Yildiz
Department of Cardiology, Faculty of Medicine, Marmara University, Selimiye M. Tibbiye C. No. 38, Haydarpasa, 34668 Istanbul, Turkey.
Pinar
P
Kuru
Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey.
Ebru
E
Toksoy Oner
Department of Cardiology, Faculty of Medicine, Marmara University, Selimiye M. Tibbiye C. No. 38, Haydarpasa, 34668 Istanbul, Turkey.
Mehmet
M
Agirbasli
D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D009203:Myocardial Infarction / Q000097:blood / Q000235:genetics* / Q000473:pathology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use; D055550:Protein Stability; D010959:Tissue Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000235:genetics; D020246:Venous Thrombosis / Q000097:blood / Q000235:genetics* / Q000473:pathology
D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator