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The Scientific World Journal
Volume 2014, Article ID 858293, 11 pages
http://dx.doi.org/10.1155/2014/858293
Review Article

Functional Stability of Plasminogen Activator Inhibitor-1

1Department of Bioengineering, Marmara University, 34722 Istanbul, Turkey
2Department of Cardiology, Faculty of Medicine, Marmara University, Selimiye M. Tibbiye C. No. 38, Haydarpasa, 34668 Istanbul, Turkey

Received 30 July 2014; Accepted 17 September 2014; Published 15 October 2014

Academic Editor: Nejat Akar

Copyright © 2014 Songul Yasar Yildiz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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.