RT Journal Article SR Electronic T1 Effect of Bosentan on Plasma Markers of Endothelial Cell Activity in Patients with Secondary Pulmonary Hypertension Related to Connective Tissue Diseases JF The Journal of Rheumatology JO J Rheumatol FD The Journal of Rheumatology SP jrheum.080542 DO 10.3899/jrheum.080542 A1 Giuseppe Cella A1 Fabrizio Vianello A1 Franco Cozzi A1 Helga Marotta A1 Francesco Tona A1 Graziella Saggiorato A1 Omer Iqbal A1 Jawed Fareed YR 2009 UL http://www.jrheum.org/content/early/2009/01/22/jrheum.080542.abstract AB Objective To evaluate plasma markers of endothelial cell activity in patients with pulmonary arterial hypertension (PAH) induced by connective tissue diseases (CTD) before and after 3-month administration of bosentan. Methods We quantified E, L and P-selectin (sE-S, sL-S, sP-S), thrombomodulin (TM), monocytechemotactic protein 1 (MCP-1), human soluble CD40 ligand (sCD40L), and nitric oxide (NO) in 18 patients and 18 controls. We evaluated right ventricular systolic pressure (RVSP) and the 6-minute walk test (6-MWT). Results All plasma markers but sL-S and TM at Time 0 were significantly higher in patients compared with controls. After 3 months of therapy, decreased levels were noted in NO (Time 0 24.05 ± 6.01 mmol/l, Time 1 13.92 ± 3.40 mmol/l; p < 0.001) and sCD40L (Time 0 1685.33 ± 866 pg/ml, Time 1 1055.11 ± 630.6 pg/ml; p = 0.017). In contrast, sP-S was significantly increased (Time 0 88.36 ± 47.76 ng/ml, Time 1 147.21 ± 94.43 ng/ml; p = 0.021).All patients remained stable inWHO class III, and in 9 patients we noted an improvement in 6-MWT. A correlation was found between Δ of RVSP and 6-MWT (r2 = 0.5355, p < 0.001) as well as between Δ-sP-S and both Δ-6-MWT and Δ-RVSP.An increase sP-S level was found in 89% of nonresponder patients, whereas 55% of responders showed a stable or reduced sP-S level (p = 0.016 responder vs nonresponder). Conclusion Treatment with bosentan for 3 months induced a beneficial effect by restoring endothelial function through a decrease in the markers of endothelial cell activity, leading to stabilization or improvement of severe PAH.