Ambient oxygen tension modulates endothelial fibrinolysis.
OBJECTIVE
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 (PAI-1) 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 Po2 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 increases or decreases % change, normalized for cell count, versus controls, were analyzed by enzyme-linked immunosorbent assay. Cellular tPA and PAI-1 mRNAs were assessed by Northern analysis.


RESULTS
The tPA but not PAI-1 was significantly decreased after the first 24 hours 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 Po2 of 40 mm Hg, returning to baseline within 24 hours of Po2 to 150 mm Hg restoration.


CONCLUSIONS
These data support the hypothesis of a fibrinolytic shift after altered ambient O2 tensions exposure in endothelium and demonstrate that HSVEC are more sensitive to altered O2 tension than HUVEC. Altered O2 tensions depress EC fibrinolysis in this model.
Gertler
J P
JP
Division of Vascular Surgery, Massachusetts General Hospital, Boston 02114.
Perry
L
L
L'Italien
G
G
Chung-Welch
N
N
Cambria
R P
RP
Orkin
R
R
Abbott
W M
WM
D001274:Atmospheric Pressure; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D010100:Oxygen / Q000494:pharmacology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D012501:Saphenous Vein / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000187:drug effects* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects*
D017077:Culture Media, Conditioned; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010959:Tissue Plasminogen Activator; D010100:Oxygen