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MMPs, inflammation and pulmonary arterial hypertension
Pulmonary arterial hypertension (PAH) is characterised by remodelling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure [1]. PAH can be idiopathic, familial, or associated with a number of conditions or diseases, such as conn...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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2008
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122977/ http://dx.doi.org/10.1007/978-3-7643-8585-9_6 |
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author | d’Ortho, Marie-Pia |
author_facet | d’Ortho, Marie-Pia |
author_sort | d’Ortho, Marie-Pia |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is characterised by remodelling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure [1]. PAH can be idiopathic, familial, or associated with a number of conditions or diseases, such as connective tissue disease. Its prognosis is poor, less than 3 yr from diagnosis. The aetiology of severe unexplained pulmonary hypertension remained largely unknown until a few years ago. The gene underlying familial PAH was identified in 2000, the BMPR-2 gene. However its mutations are not always present, and it probably does not explained the full scope of the disease. PAH is associated with structural alterations in pulmonary arteries including intimal fibrosis, medial hypertrophy and adventitial changes, pointing towards extracellular matrix remodelling which have raised the question of involvement of the matrix degrading enzymes. Among them, serine proteases, such as plasmina and endogenous vascular elastase (EVE), and matrix metalloproteases have been studied. In experimental models, the three of them are increased. Accordingly, their inhibition has preventing and in some cases therapeutic effects. However it should be stressed that opposite consequence of protease inhibition on PAH can be observed depending on the experimental model, either chronic hypoxia-induced PAH (deleterious) or toxic moncrotalin-induced PAH (positive). In humans, only sparse reports exist, that found increase in the MMP inhibitor, TIMP-1, and MMP-2 expression and decreased collagenase (MMP-1). Inflammation is part of the PAH, and accordingly, protease production is a well known part of the inflammatory response. Answering the question whether protease inhibition might represent a therapeutic option in human PAH is however certainly too early. |
format | Online Article Text |
id | pubmed-7122977 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2008 |
record_format | MEDLINE/PubMed |
spelling | pubmed-71229772020-04-06 MMPs, inflammation and pulmonary arterial hypertension d’Ortho, Marie-Pia Matrix Metalloproteinases in Tissue Remodelling and Inflammation Article Pulmonary arterial hypertension (PAH) is characterised by remodelling of small pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and right ventricular failure [1]. PAH can be idiopathic, familial, or associated with a number of conditions or diseases, such as connective tissue disease. Its prognosis is poor, less than 3 yr from diagnosis. The aetiology of severe unexplained pulmonary hypertension remained largely unknown until a few years ago. The gene underlying familial PAH was identified in 2000, the BMPR-2 gene. However its mutations are not always present, and it probably does not explained the full scope of the disease. PAH is associated with structural alterations in pulmonary arteries including intimal fibrosis, medial hypertrophy and adventitial changes, pointing towards extracellular matrix remodelling which have raised the question of involvement of the matrix degrading enzymes. Among them, serine proteases, such as plasmina and endogenous vascular elastase (EVE), and matrix metalloproteases have been studied. In experimental models, the three of them are increased. Accordingly, their inhibition has preventing and in some cases therapeutic effects. However it should be stressed that opposite consequence of protease inhibition on PAH can be observed depending on the experimental model, either chronic hypoxia-induced PAH (deleterious) or toxic moncrotalin-induced PAH (positive). In humans, only sparse reports exist, that found increase in the MMP inhibitor, TIMP-1, and MMP-2 expression and decreased collagenase (MMP-1). Inflammation is part of the PAH, and accordingly, protease production is a well known part of the inflammatory response. Answering the question whether protease inhibition might represent a therapeutic option in human PAH is however certainly too early. 2008 /pmc/articles/PMC7122977/ http://dx.doi.org/10.1007/978-3-7643-8585-9_6 Text en © Birkhäuser Verlag Basel/Switzerland 2008 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic. |
spellingShingle | Article d’Ortho, Marie-Pia MMPs, inflammation and pulmonary arterial hypertension |
title | MMPs, inflammation and pulmonary arterial hypertension |
title_full | MMPs, inflammation and pulmonary arterial hypertension |
title_fullStr | MMPs, inflammation and pulmonary arterial hypertension |
title_full_unstemmed | MMPs, inflammation and pulmonary arterial hypertension |
title_short | MMPs, inflammation and pulmonary arterial hypertension |
title_sort | mmps, inflammation and pulmonary arterial hypertension |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122977/ http://dx.doi.org/10.1007/978-3-7643-8585-9_6 |
work_keys_str_mv | AT dorthomariepia mmpsinflammationandpulmonaryarterialhypertension |