The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn).
OBJECTIVE
To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor 1 (PAI-1) and tissue plasminogen activator (t-PA) plasma levels in SSc patients (pts) versus healthy controls and their modulation by intravenous alphacyclodestrine (Alprostadil).


METHODS
Plasma levels of u-PA, su-PAR, PAI-1 and t-PA were measured in 40 SSc (34 lSSc and 6 dSSc) pts and in 30 healthy controls. In SSc, blood was drawn before and after 3 consecutive daily of Alprostadil infusion (60 mg in 250 cc NaCl 0.9%).


RESULTS
In SSc su-PAR basal levels were higher than controls (7.48 +/- 2.5 vs 4.69 +/- 0.4 ng/ml; p = 0.001) and were significantly reduced by Alprostadil (5.93 +/- 1.7; p = 0.002), but remain higher than controls (p = 0.03). u-PA basal levels were higher than controls (3.78 +/- 1.5 vs 1.29 +/- 0.3 ng/ml; p < 0.001) and were reduced by Alprostadil (2.39 +/- 1.7; p < 0.001) to control levels. SSc PAI-1 basal levels were lower than controls (31.60 +/- 7.7 vs 48.30 +/- 6.8 ng/ml; p < 0.001) and increased by Alprostadil (34.66 +/- 5.4; p = 0.04), but lower than controls (p < 0.001). SSc t-PA basal levels were higher in respect to controls (1645.81 +/- 792.7 vs 571.95 +/- 75.5 pg/ml; p < 0.0001) and reduced by Alprostadil (1318.06 +/- 603.5; p = 0.04), but still higher than controls (p = 0.001).


CONCLUSIONS
Fibrinolysis were increased in SSc. Infusions of Alprostadil modulate u-PA, su-PAR, PAI-1 and t-PA, restoring near normal levels. In SSc, fibrinolysis system may become a potential target for new therapies.
Bandinelli
F
F
Department of Medicine, Division of Rheumatology, University of Florence, Florence, Italy.
Bartoli
F
F
Perfetto
E
E
Del Rosso
A
A
Moggi-Pignone
A
A
Guiducci
S
S
Cinelli
M
M
Fatini
C
C
Generini
S
S
Gabrielli
A
A
Giacomelli
R
R
Maddali Bongi
S
S
Abbate
R
R
Del Rosso
M
M
Matucci Cerinic
M
M
D000368:Aged; D000527:Alprostadil / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011956:Receptors, Cell Surface / Q000097:blood; D055293:Receptors, Urokinase Plasminogen Activator; D012595:Scleroderma, Systemic / Q000097:blood / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D005343:Fibrinolytic Agents; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D000527:Alprostadil