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

F. Bandinelli¹, F. Bartoli¹, F. Perfetto¹, A. Del Rosso¹, A. Moggi-Pignone¹, S. Guiducci¹, M. Cinelli¹, C. Fatini², S. Generini¹, A. Gabrielli³, R. Giacomelli⁴, S. Maddali Bongi¹, R. Abbate², M. Del Rosso⁵, M. Matucci Cerinic¹

¹Department of Medicine, Division of Rheumatology and ²Dipartimento del Cuore e dei Vasi, University of Florence; ³Istituto di Clinica Medica Generale, Ematologia ed Immunologia Clinica, Università Politecnica delle Marche, Ancona; ⁴Department of Internal Medicine, University of L’Aquila, L’Aquila, Italy; ⁵Dipartimento di Patologia e Oncologia Sperimentali, University of Florence, Florence, Italy.

ABSTRACT
Objectives
To evaluate urokinase plasminogen activator (u-PA), urokinase plasminogen activator soluble receptor (su-PAR), plasminogen activator inhibitor I (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).

Conclusion
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.

Key words
Fibrinolysis, systemic sclerosis, prostaglandins.

Please address correspondence to: Professor M Matucci Cerinic, Department of Medicine, Division of Rheumatology, University of Florence, Viale G. Pieraccini no. 18, 50139 Florence, Italy.
E-mail: cerinic@unifi.it

Clin Exp Rheumatol 2005; 23: 671-677.
© CLINICAL AND EXPERIMENTAL RHEUMATOLOGY 2005.