The fibrinolytic system components are increased in systemic sclerosis and modulated by Alprostadil (alpha1 ciclodestryn)

• Published in: Clinical and experimental rheumatology 2005-09, Vol.23 (5), p.671-677
• Main Authors: BANDINELLI, F, BARTOLI, F, GIACOMELLI, R, BONGI, S. Maddali, ABBATE, R, DEL ROSSO, M, CERINIC, M. Matucci, PERFETTO, F, DEL ROSSO, A, MOGGI-PIGNONE, A, GUIDUCCI, S, CINELLI, M, FATINI, C, GENERINI, S, GABRIELLI, A
• Format: Article
• Language: English
• Subjects: Aged; Alprostadil - pharmacology; Alprostadil - therapeutic use; Biological and medical sciences; Diseases of the osteoarticular system; Female; Fibrinolysis - drug effects; Fibrinolytic Agents - pharmacology; Fibrinolytic Agents - therapeutic use; Humans; Male; Medical sciences; Middle Aged; Plasminogen Activator Inhibitor 1 - blood; Receptors, Cell Surface - blood; Receptors, Urokinase Plasminogen Activator; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Scleroderma, Systemic - blood; Scleroderma, Systemic - drug therapy; Tissue Plasminogen Activator - blood; Urokinase-Type Plasminogen Activator - blood
• ISSN: 0392-856X; 1593-098X

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). 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%). 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). 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.