The status of plasminogen activator inhibitor-1 as a therapeutic target.
Plasminogen activator inhibitor-1 (PAI-1) is the major physiological inhibitor of tissue-type plasminogen activator (tPA). An increase in the plasma concentration of PAI-1 has been proposed as a risk factor in thrombotic disease and elevated PAI-1 is associated with a poor prognosis in a variety of cancers. These observations have led to numerous studies addressing the physiological and pathophysiological role of PAI-1 and to the proposal that manipulation of PAI-1 activity presents a new therapeutic target. Recent experimental studies with anti-PAI-1 antibodies and low molecular weight inhibitors have demonstrated efficacy in both arterial and venous thrombosis models. These studies have confirmed the potential clinical benefit of reducing PAI-1 activity. As it is now possible to manipulate PAI-1 activity in vivo, future studies should be aimed at confirming the importance of PAI-1 as a major therapeutic target.
Charlton
P
P
Xenova Limited, 240 Bath Road, Slough, Berkshire, SL1 4EF, UK.