Tissue-type plasminogen activator release: new frontiers in endothelial function.

Tissue-type plasminogen activator (t-PA) is a pivotal enzyme in the mammalian fibrinolytic system. It exerts its action by converting the zymogen plasminogen into the proteolytically active serine protease plasmin, which, in turn, degrades fibrin clots. Because of its affinity for fibrin, t-PA is the prototypic fibrin-specific plasminogen activator (1). This specificity and its lack of antigenicity have made it a powerful tool in the treatment of acute myocardial infarction (2). The t-PA is inactivated by its suicide substrate, plasminogen activator inhibitor-1 (PAI-1) (3). Storage of t-PA in endothelial cells. The t-PA is synthesized and stored in endothelial cells and vascular neurons (4,5). There has been much controversy in the published data regarding the specific endothelial cell vesicle in which t-PA is stored. It has been suggested that because t-PA is often released concomitantly with von Willebrand factor (vWF), both proteins are stored in Weibel-Palade bodies. Emeis et al. (6) demonstrated that this is not necessarily the case. In studies using rat lung homogenates fractionated by