Fig. 1

Expression of tissue plasminogen activator and plasminogen activator inhibitor-1 expression in porcine-to-baboon cardiac xenografts. Tissue samples obtained from porcine hearts and porcine cardiac xenografts were studied by immunofluorescence for expression of tissue plasminogen activator and plasminogen activator inhibitor-1. (A) Normal porcine cardiac tissue stained for tissue plasminogen activator demonstrates staining throughout the cardiac microvasculature. (B) Normal porcine cardiac tissue stained for plasminogen activator inhibitor-1 demonstrates no detectable fluorescence above background. Hearts of transgenic pigs expressing human CD59 and decay accelerating factor were transplanted into baboons, and tissue biopsies were taken post-transplant. Cardiac xenografts with acute vascular rejection revealed a dramatic decrease in tissue plasminogen activator expression (C) and a significant increase in expression of plasminogen activator inhibitor-1 (D). ×20. The increase in plasminogen activator inhibitor-1 is distributed along the vascular endothelium. The changes occurred prior to histologic evidence of acute vascular rejection. This suggests that the depletion of tissue plasminogen activator and up-regulation of plasminogen activator inhibitor-1 contribute early to the pathogenesis of thrombosis seen in acute vascular rejection, and are not merely the result of tissue injury after acute vascular rejection has commenced.