TY - JOUR 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 DO - 10.3899/jrheum.080542 SP - jrheum.080542 AU - Giuseppe Cella AU - Fabrizio Vianello AU - Franco Cozzi AU - Helga Marotta AU - Francesco Tona AU - Graziella Saggiorato AU - Omer Iqbal AU - Jawed Fareed Y1 - 2009/01/15 UR - http://www.jrheum.org/content/early/2009/01/22/jrheum.080542.abstract N2 - 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. ER -