Document Detail


Effect of bosentan on plasma markers of endothelial cell activity in patients with secondary pulmonary hypertension related to connective tissue diseases.
MedLine Citation:
PMID:  19208592     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Giuseppe Cella; Fabrizio Vianello; Franco Cozzi; Helga Marotta; Francesco Tona; Graziella Saggiorato; Omer Iqbal; Jawed Fareed
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-22
Journal Detail:
Title:  The Journal of rheumatology     Volume:  36     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-04-03     Completed Date:  2009-06-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  760-7     Citation Subset:  IM    
Affiliation:
Department of Medical Sciences, University of Padova Medical Schoo, Via Ospedale Civile 105, 35100 Padova, Italy. giuseppe.cella@unipd.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antihypertensive Agents / therapeutic use*
Biological Markers / blood*
Connective Tissue Diseases / complications*,  physiopathology
Disease Progression
Endothelial Cells / metabolism*
Endothelium, Vascular* / cytology,  physiopathology
Exercise Test
Female
Humans
Hypertension, Pulmonary / blood*,  drug therapy*,  etiology*,  physiopathology
Male
Middle Aged
Sulfonamides / therapeutic use*
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Biological Markers; 0/Sulfonamides; 147536-97-8/bosentan
Comments/Corrections
Comment In:
J Rheumatol. 2009 Apr;36(4):665-6   [PMID:  19342719 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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