The pathophysiological relevance of PAI-1 in cardiovascular diseases and the development of monoclonal antibodies as PAI-1 inhibitors.

Plasminogen activator inhibitor- (PAI-1) is an important component of the plasminogen/plasmin system as it is the main inhibitor of tissue-type (t-PA) and urokinase-type plasminogen activator (u-PA). Consequently, PAI-1 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-1 shares important structural properties with other serpins. However, PAI-1 also exhibits unique conformational and functional properties. The current review provides an overview of the knowledge on PAI-1 gathered since its discovery two decades ago. We are discussing (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) the development of monoclonal antibodies aiming to modulate pharmacologically this risk factor.