AMBIENT OXYGEN-TENSION MODULATES ENDOTHELIAL FIBRINOLYSIS

Purpose: Vascular procedures reoxygenate ischemic endothelial cells (EC) and arterialize saphenous vein (HSV) EC. The balance between the EC-derived fibrinolytic components, plasminogen activator (tPA), and plasminogen inhibitor (PAZ-I) contributes to maintaining thromboresistance. This balance also affects proteolysis through plasmin generation, mediating matrix metabolism endothelial migration, angiogenesis, and theoretically affecting the development of intimal hyperplasia. Methods: To explore the impact of varying oxygen tensions on EC fibrinolysis, HSV and human umbilical vein (HUV) were subjected to PO2 of 40 mm Hg for 24 hours with restoration of Po, to 150 mm Hg for 24 hours. The tPA and PAI-1 antigen and tPA/PAI-1 antigen ratio in conditioned media (CM), expressed as up arrow or down arrow % change, normalized for cell count, versus controls, were analyzed by enzyme-linked immunosorbent assay. Cellular tPA and PAI-I mRNAs were assessed by Northern analysis. Results: The tPA but not PAT-1 was significantly decreased after the first 24 hows in HSVEC and significantly decreased after 48 hours in both HUVEC and HSVEC when compared with controls. Messenger RNA for tPA was unchanged but PAI-1 mRNA increased significantly for HSVEC and HUVEC after 24 hours of Po, of 40 mm Hg, returning to baseline within 24 hours of Po-2 to 150 mm Hg restoration. Conclusions: These data support the hypothesis of a fibrinolytic shift after altered ambient O-2 tensions exposure in endothelium and demonstrate that HSVEC are more sensitive to altered O-2 tension than HUVEC. Altered O-2 tensions depress EC fibrinolysis in this model.