REGULATION OF PLASMINOGEN ACTIVATORS IN CONNECTIVE TISSUES - POTENTIAL FOR THROMBOLYTIC THERAPY IN COLLAGEN-VASCULAR DISEASES

Cells in connective tissues such as skin, lung, ligaments, tendons, cartilage, synovium and intravertebral discs express plasminogen activators (PA) and plasminogen activator inhibitors (PAI) in a highly regulated fashion. Such PA and PAI very likely play a role in normal tissue maturation, tissue remodelling, and tissue repair. Dysregulation of this system can contribute to tissue degradation and loss of function. Alterations in regulation have been shown to occur locally in tissues such as joints (rheumatoid arthritis and osteoarthritis) or in lungs (acute respiratory distress syndrome and fibrotic lung disease), as well as systemically in inflammatory diseases such as scleroderma, systemic lupus erythematosus or rheumatoid arthritis. The dysfunction of the PA/PAI system in such diseases raises the possibility that thrombolytics such as urokinase or tissue plasminogen activator may have efficacy in inhibiting disease progression and reversing some disease associated alterations.