Plasminogen Activator Inhibitor 1 (PAI-1) Activity

Plasminogen activator inhibitor 1 (PAI-1) is a member of a family of proteins that inhibit plasminogen activators.^6-8 PAI-1 is a single-chain glycoprotein with a molecular weight of 47 kilodaltons. During fibrinolysis, tissue plasminogen activator (tPA) converts the inactive protein plasminogen into plasmin. Plasmin, in turn, plays a critical role in fibrinolysis by degrading fibrin and also provides localized protease activity in a number of physiological functions, including ovulation, cell migration, and epithelial cell differentiation. PAI-1 is the primary inhibitor of tPA and other plasminogen activators in the blood. PAI-1 limits the production of plasmin and serves to keep fibrinolysis in check. Uncontrolled plasmin production can result in excessive degradation of fibrin and an increased risk of bleeding. PAI-1 levels are, in part, controlled on a genetic basis.⁶ Certain polymorphisms in the PAI-1 gene are associated with increased blood concentrations. Increased PAI-1 levels have been shown to be associated with a number of atherosclerotic risk factors.^6,7 Insulin and proinsulin correlate with PAI-1 levels. Patients with insulin resistance syndrome and diabetes mellitus tend to have increased PAI-1 levels. Weight loss and treatment aimed at lowering triglyceride and/or cholesterol levels have also been shown to lower PAI-1 levels. PAI-1 has been shown to act as a prothrombic factor in both arterial and venous thromboembolic disorders.^6,7 Increased levels of PAI-1 are associated with an increased incidence of acute coronary syndrome. PAI-1 levels are also increased in patients with chronic and acute coronary artery disease (CAD) and in patients who suffer restenosis after coronary angioplasty. It has also been shown that increased PAI-1 levels may reduce the effectiveness of antithrombolytic therapy.^6,8 In fact, certain fibrinolytic agents, such as TNK-t-PA, are PAI-1-resistant and may be more effective in patients with increased PAI-1 levels. The method used for measuring PAI-1 activity in this test is an immunoassay that is specific for proteins that bind to tissue plasminogen activator (tPA) immobilized on a microtiter plate. The bound protein is then quantified using a monoclonal antibody that is specific for PAI-1. The assay is highly specific for protein recognized by the PAI-1 antibody that also has the ability to bind to tPA. Proteins with these characteristics are the predominant inhibitors of plasminogen activation in serum.⁶