The structural basis for the pathophysiological relevance of PAl-l in cardiovascular diseases and the development of potential PAl-l inhibitors

被引：83

作者：

Gils, A ^{[1
]}

Declerck, PJ ^{[1
]}

机构：

[1] Catholic Univ Louvain, Fac Pharmaceut Sci, Lab Pharmaceut Biol & Phytopharmacol, B-3000 Louvain, Belgium

来源：

THROMBOSIS AND HAEMOSTASIS | 2004年 / 91卷 / 03期

关键词：

PAl-l; serpin; fibrinolysis; thrombosis;

D O I：

10.1160/TH03-12-0764

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Plasminogen activator inhibitor-I (PAI-I) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type and urokinase-type plasminogen activator. Consequently, PAI-I plays an important role in cardiovascular diseases (mainly through inhibition of t-PA), and in cell migration and tumor development (mainly through inhibition of u-PA and interaction with vitronectin). As a member of the serpin superfamily, PAI-I shares important structural properties with other serpins. However, PAI-I also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-I gathered,since its discovery two decades ago. We discuss (a) its structural properties of the protein and their subsequent relation to functional activities, (b) its role in a wide variety of (patho)physiological processes and (c) a number of strategies to interfere with its functional properties eventually aiming at pharmacological modulation of this risk factor.

引用

页码：425 / 437

页数：13

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