THIOL ISOMERASES – A POSSIBLE TARGET FOR THROMBOSIS CONTROL

Abstract

While there are an increasing number of antithrombotic agents with demonstrated clinical efficacy, thrombosis remains the leading cause of mortality in developed countries. Therefore, there is a need further development of therapies targeting alternative components of the blood clotting mechanism, based on new knowledge about the mechanisms of thrombus formation. Recently, among several unexpected findings of new methods and approaches to the study of these mechanisms it was discovered that protein disulfide isomerase (PDI) serves an essential role in the processes of thrombus formation. PDI is secreted by platelets and endothelial cells following activation and localizes to the membrane surface. Given the role of PDI in regulating both platelet aggregation and fibrin generation in vivo , the possibility of using PDI as an antithrombotic target is discussed. While most antithrombotic target either platelet or coagulation activation, PDI inhibitors have the potential to prevent thrombosis in conditions with pathologic activation of both pathways as implicated in complex thrombotic disorders such as myocardial infarction and cancer associated thrombosis. This review considers what is known about the role of PDI in thrombus formation, main targets and mechanisms of action, as well as PDI inhibitors, as candidates for a new class of antithrombotic agents with both antiplatelet and anticoagulant properties to prevent thrombosis in humans.