AMBIENT OXYGEN-TENSION MODULATES ENDOTHELIAL FIBRINOLYSIS

Purpose: Vascular procedures reoxygenate ischemic endothelial cells (E C) and arterialize saphenous vein (HSV) EC. The balance between the EC -derived fibrinolytic components, plasminogen activator (tPA), and pla sminogen inhibitor (PAZ-I) contributes to maintaining thromboresistanc e. This balance also affects proteolysis through plasmin generation, m ediating matrix metabolism endothelial migration, angiogenesis, and th eoretically 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 f or 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 (C M), expressed as up arrow or down arrow % change, normalized for cell count, versus controls, were analyzed by enzyme-linked immunosorbent a ssay. 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 b oth HUVEC and HSVEC when compared with controls. Messenger RNA for tPA was unchanged but PAI-1 mRNA increased significantly for HSVEC and HU VEC 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 suppo rt the hypothesis of a fibrinolytic shift after altered ambient O-2 te nsions exposure in endothelium and demonstrate that HSVEC are more sen sitive to altered O-2 tension than HUVEC. Altered O-2 tensions depress EC fibrinolysis in this model.