Rheumatology

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Effect of bosentan on plasma markers of endothelial cell activity in patients with secondary pulmonary hypertension related to connective tissue diseases
Journal of Rheumatology, 04/10/09

Cella G et al. – Study demonstrates that 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 pulmonary arterial hypertension (PAH).

• Aim was to evaluate plasma markers of endothelial cell activity in patients with PAH-induced by connective tissue diseases (CTD) before and after 3-mo administration of bosentan
• Molecules quantified in 18 pts and 18 controls:
  • 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)
• Right ventricular systolic pressure (RVSP) and the 6-minute walk test (6-MWT) was evaluated

• All plasma markers but sL-S and TM at Time 0 were higher in pts vs controls
• After 3 mo of therapy, decreased levels were noted in NO and sCD40L
• In contrast, sP-S was increased
• All pts remained stable in WHO class III
• In 9 pts there was an improvement in 6-MWT
• A correlation was found between Δ of RVSP and 6-MWT, 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 pts
• 55% of responders showed a stable or reduced sP-S level

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