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), monocyte-chemotactic 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 in WHO class III, and in 9 patients we noted an improvement in 6-MWT. A correlation was found between Delta of RVSP and 6-MWT (r2=0.5355, p<0.001) as well as between Delta-sP-S and both Delta-6-MWT and Delta-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.
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), monocyte-chemotactic 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 in WHO class III, and in 9 patients we noted an improvement in 6-MWT. A correlation was found between Delta of RVSP and 6-MWT (r2=0.5355, p<0.001) as well as between Delta-sP-S and both Delta-6-MWT and Delta-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.
Authors: Manuel J Richter; Ralph Schermuly; Werner Seeger; Youlan Rao; Hossein A Ghofrani; Henning Gall Journal: Pulm Circ Date: 2016-12 Impact factor: 3.017
Authors: Jason M Elinoff; J Eduardo Rame; Paul R Forfia; Mary K Hall; Junfeng Sun; Ahmed M Gharib; Khaled Abd-Elmoniem; Grace Graninger; Bonnie Harper; Robert L Danner; Michael A Solomon Journal: Trials Date: 2013-04-02 Impact factor: 2.279