Document Detail


The effect of bosentan on matrix metalloproteinase-9 levels in patients with systemic sclerosis-induced pulmonary hypertension.
MedLine Citation:
PMID:  15811199     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Systemic sclerosis (SSc) is an autoimmune disease that can potentially involve all tissues and organs of the human body. Based on the extent of the disease and organ involvement, different subsets of patients and organ involvement, different subsets of patients have been identified and several classifications proposed have been identified and several classifications proposed aiming to better stratify affected patients. The occurrence aiming to better stratify affected patients. The occurrence of pulmonary arterial hypertension (PAH), characterized of pulmonary arterial hypertension (PAH), characterized by altered tissue remodelling of the entire vessel wall, is the most severe complication that influences prognosis and survival. The molecular basis underlying the vascular damage is not yet known, but a family of enzymes named matrix metalloproteinases (MMPs), with a proteolytic activity towards several extra-cellular matrix (ECM) components, is likely to be involved. Recently, a dual inhibitor of endothelin-1, bosentan, has been successfully evaluated in clinical trials in PAH patients. Research design and method: The aim of this study is to investigate the expression of MMP-2 and MMP-9 in the serum of different subsets of SSc patients, and in patients treated with bosentan. Thirty-five Caucasian patients with SSc were enrolled in the study, 12 of whom were found to have isolated PAH assessed by Doppler echocardiography. Eight patients fully met the inclusion criteria and were eligible for therapy with bosentan given at the dosage of 62.5 mg twice daily for 4 weeks followed by 125 mg twice daily for 50 weeks(15). The remaining patients (4/12) initiated bosentan therapy for a few weeks and, therefore, were considered at the baseline level only. Serum samples were analysed by gelatine zymography.
RESULTS: The results suggest that MMP-9 but not MMP-2 is differently expressed according to the degree of organ involvement. In particular, MMP-9 serum levels are significantly decreased in PAH with respect to other subsets of SSc patients. Moreover, in bosentan-treated patients, after 12 months of therapy MMP-9 significantly (p < 0.05) increased and correlated with an improved clinical outcome, as measured by the '6-minutes walking' test.
CONCLUSIONS: This is the first time that MMP-9 serum levels are reported to be down-regulated in PAH patients and up-regulated following bosentan treatment. Whether MMP-9 has a pathogenetic role in the vascular damage observed in PAH patients or it is a marker of bosentan effectiveness is not yet known. However, MMP-9 may be an important molecule that needs further investigation in SSc patients to better define its role.
Authors:
Gianluigi Giannelli; Florenzo Iannone; Felice Marinosci; Giovanni Lapadula; Salvatore Antonaci
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Publication Detail:
Type:  Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Current medical research and opinion     Volume:  21     ISSN:  0300-7995     ISO Abbreviation:  Curr Med Res Opin     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-04-06     Completed Date:  2005-07-05     Revised Date:  2013-06-18    
Medline Journal Info:
Nlm Unique ID:  0351014     Medline TA:  Curr Med Res Opin     Country:  England    
Other Details:
Languages:  eng     Pagination:  327-32     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Immunology and Infectious Diseases, Section of Internal Medicine, University of Bari Medical School, Bari, Italy. g.giannelli@intmed.uniba.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antihypertensive Agents / therapeutic use*
Female
Humans
Hypertension, Pulmonary / drug therapy*,  etiology
Male
Matrix Metalloproteinase 2 / biosynthesis,  blood
Matrix Metalloproteinase 9 / biosynthesis*,  blood
Middle Aged
Scleroderma, Systemic / complications*
Sulfonamides / therapeutic use*
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 0/Sulfonamides; EC 3.4.24.24/Matrix Metalloproteinase 2; EC 3.4.24.35/Matrix Metalloproteinase 9; Q326023R30/bosentan

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