title: Effect of bosentan on plasma markers of endothelial cell activity in patients with secondary pulmonary hypertension related to connective tissue diseases.
abstract: 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).
  
  
  CONCLUSIONS
  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.affiliation: Department of Medical Sciences, University of Padova Medical Schoo, Via Ospedale Civile 105, 35100 Padova, Italy. giuseppe.cella@unipd.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cella
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vianello
authors.forename: Franco
authors.initials: F
authors.lastname: Cozzi
authors.forename: Helga
authors.initials: H
authors.lastname: Marotta
authors.forename: Francesco
authors.initials: F
authors.lastname: Tona
authors.forename: Graziella
authors.initials: G
authors.lastname: Saggiorato
authors.forename: Omer
authors.initials: O
authors.lastname: Iqbal
authors.forename: Jawed
authors.initials: J
authors.lastname: Fareed
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D000077300:Bosentan; D003240:Connective Tissue Diseases / Q000150:complications* / Q000503:physiopathology; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000503:physiopathology; D005080:Exercise Test; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D015415:Biomarkers; D013449:Sulfonamides; D000077300:Bosentan