Coronary artero-venous gradient of endogenous urokinase.
Experimental data indicate that urokinase-type plasminogen activator (u-PA) contributes significantly to endogenous fibrinolysis and vascular remodeling in proportion to its local concentrations. In humans, however, it is not known whether u-PA levels vary at different sites and across specific vascular beds. We investigated possible regional and artero-venous differences in plasma u-PA concentrations in 15 patients undergoing cardiac catheterization. Three pairs of simultaneous samples were taken from: (1) the ascending aorta and coronary sinus; (2) left ventricle and right atrium; (3) femoral artery and femoral vein. Single-chain urokinase-type plasminogen activator (scu-PA) was measured by bioimmunoassay, and total u-PA antigen (including scu-Pa and two-chain urokinase-type plasminogen activator complexed with inhibitors (tcu-PA)) by enzyme-linked immunosorbent assay. Scu-PA represented, on average, 51+/-15% of total u-PA concentrations. Scu-PA and total u-PA levels were correlated (r=.72, P<.0001) and did not differ significantly among the arterial or venous locations. There was a small but consistent increase in mean (+/-standard deviation (S.D.)) scu-PA concentrations from all arterial to all venous samples (1.5+/-0.6 vs. 1.6+/-0.5 ng/ml, P=.038) and from ascending aorta to coronary sinus (1.6+/-0.5 vs. 1.7+/-0.6 ng/ml, P=.046). Similarly, total u-PA levels increased from femoral artery to femoral vein (2.9+/-0.7 vs. 3.0+/-0.8 ng/ml, P<.001). In contrast, across the lungs, no significant concentration-gradient was seen in either scu-PA or total u-PA. The changes in total u-PA roughly followed those of scu-PA. These data identify an artero-venous gradient in human plasma u-PA across the coronary and peripheral beds, but not across the lungs, suggesting differences in u-PA kinetics according to vascular location.
Andreotti
F
F
Institute of Cardiology, Catholic University, Rome, Italy. felicita.andreotti@iol.it
Patrizi
R
R
Buffon
A
A
Crea
F
F
Maseri
A
A
Kluft
C
C
Dooijewaard
G
G
D000368:Aged; D001158:Arteries / Q000201:enzymology; D001769:Blood / Q000378:metabolism; D001775:Blood Circulation / Q000502:physiology; D006328:Cardiac Catheterization; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D021122:Protein Subunits; D014018:Tissue Distribution; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood*; D014680:Veins / Q000201:enzymology
D021122:Protein Subunits; D014568:Urokinase-Type Plasminogen Activator