Expression of the plasminogen activator system in the vascular wall

The aim of this project was to confirm and extend previous work on this subject by studying the expression of t-PA, u-PA, PAI-1 and uPAR in the walls of human arteries and veins as well as in rabbit iliac arteries that were normal or undergoing neointima formation.;In normal human internal mammary arteries and saphenous veins, immunohistochemistry showed all four proteins to be associated with endothelial cells with little present on smooth muscle cells. Surgical distension of saphenous veins resulted in increased immunostaining to all four proteins probably due to extravasation, as specific mRNA levels were lower in the distended compared to undistended vessels. Human atheroma demonstrated intense immunostaining to all four proteins in keeping with the increased antigens on immunoassay, increased (uPA and PAI-1) mRNA on quantitative RTPCR, and greater signal (for tPA, uPA and PAI-1) with in situ hybridisation compared to normal artery. Although PAI-1 antigen was increased in atheroma, PAI-1 activity was decreased. In human saphenous vein grafts or saphenous vein in organ culture, tPA, uPA and uPAR immunostaining was increased compared to normal undistended saphenous vein in keeping with increased signal for tPA and uPA mRNA on in situ hybridisation. PAI-1 immunostaining and mRNA signal was prominent on the endothelial cells of venous hyperplastic vessels but unlike arterial atheroma, they were largely absent on the neointimal smooth muscle cells. Experimental angioplasty of rabbit iliac arteries resulted in increased immunostaining for all four proteins and an increase in uPA activity.;These results are compatible with and extend previous reports implicating the plasminogen activator system in the control of cell migration and matrix remodelling during normal and pathological vessel growth and repair, but also emphasize the complexity of this process.