Gelatinase expression and proteolytic activity in giant-cell arteritis

Objectives: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis (GCA) and are thought to play a role in vessel disruption. However, their activation status and enzymatic activity have not been evaluated. Our aim was to investigate the distribution and proteolytic activity of gelatinase...

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Autores: Segarra Blasco, Marta, García Martínez, Ana, Sánchez, Montse, Hernández Rodríguez, José, Lozano Garcia, Ester, Grau Junyent, Josep M. (Josep Maria), Cid Xutglà, M. Cinta
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/22456
Acesso em linha:https://hdl.handle.net/2445/22456
Access Level:acceso abierto
Palavra-chave:Arteritis de cèl·lules gegants
Enzims
Giant cell arteritis
Enzymes
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spelling Gelatinase expression and proteolytic activity in giant-cell arteritisSegarra Blasco, MartaGarcía Martínez, AnaSánchez, MontseHernández Rodríguez, JoséLozano Garcia, EsterGrau Junyent, Josep M. (Josep Maria)Cid Xutglà, M. CintaArteritis de cèl·lules gegantsEnzimsGiant cell arteritisEnzymesObjectives: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis (GCA) and are thought to play a role in vessel disruption. However, their activation status and enzymatic activity have not been evaluated. Our aim was to investigate the distribution and proteolytic activity of gelatinases in GCA lesions at different stages. Methods: Expression of MMP2, MMP9, MMP2-activator MMP14 and their natural inhibitors TIMP1 and TIMP2 was determined by real-time PCR and immunohistochemistry in temporal artery sections from 46 patients and 12 controls. MMP activation status and enzymatic activity were assessed by gelatin and film in situ zymography. Results: Vascular smooth muscle cells from normal specimens constitutively expressed pro-MMP2 and its inhibitor TIMP2 with no resulting proteolytic activity. In GCA MMP2, MMP9 and MMP14 were strongly expressed in their active form by infiltrating leucocytes. Inflamed arteries also expressed TIMP1 and TIMP2. However, the MMP9/TIMP1 and MMP2/TIMP2 ratios were higher in patients compared with controls, indicating an increased proteolytic balance in GCA which was confirmed by in situ zymography. Maximal gelatinase expression and activity occurred at the granulomatous areas surrounding the internal elastic lamina (IEL). Myointimal cells also expressed MMPs and exhibited proteolytic activity, suggesting a role for gelatinases in vascular remodelling and repair. Conclusions: GCA lesions show intense expression of gelatinases. Activators and inhibitors are regulated to yield enhanced gelatinase activation and proteolytic activity. Distribution of expression and proteolytic activity suggests that gelatinases have a major role not only in the progression of inflammatory infiltrates and vessel destruction but also in vessel repair.BMJ Group2007info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/22456Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció digital del document publicat a: http://dx.doi.org/10.1136/ard.2006.068148Annals of the Rheumatic Diseases, 2007, vol. 66, núm. 11, p. 1429-1435http://dx.doi.org/10.1136/ard.2006.068148(c) BMJ Publishing Group Ltd, 2007info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/224562026-05-27T06:46:51Z
dc.title.none.fl_str_mv Gelatinase expression and proteolytic activity in giant-cell arteritis
title Gelatinase expression and proteolytic activity in giant-cell arteritis
spellingShingle Gelatinase expression and proteolytic activity in giant-cell arteritis
Segarra Blasco, Marta
Arteritis de cèl·lules gegants
Enzims
Giant cell arteritis
Enzymes
title_short Gelatinase expression and proteolytic activity in giant-cell arteritis
title_full Gelatinase expression and proteolytic activity in giant-cell arteritis
title_fullStr Gelatinase expression and proteolytic activity in giant-cell arteritis
title_full_unstemmed Gelatinase expression and proteolytic activity in giant-cell arteritis
title_sort Gelatinase expression and proteolytic activity in giant-cell arteritis
dc.creator.none.fl_str_mv Segarra Blasco, Marta
García Martínez, Ana
Sánchez, Montse
Hernández Rodríguez, José
Lozano Garcia, Ester
Grau Junyent, Josep M. (Josep Maria)
Cid Xutglà, M. Cinta
author Segarra Blasco, Marta
author_facet Segarra Blasco, Marta
García Martínez, Ana
Sánchez, Montse
Hernández Rodríguez, José
Lozano Garcia, Ester
Grau Junyent, Josep M. (Josep Maria)
Cid Xutglà, M. Cinta
author_role author
author2 García Martínez, Ana
Sánchez, Montse
Hernández Rodríguez, José
Lozano Garcia, Ester
Grau Junyent, Josep M. (Josep Maria)
Cid Xutglà, M. Cinta
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Arteritis de cèl·lules gegants
Enzims
Giant cell arteritis
Enzymes
topic Arteritis de cèl·lules gegants
Enzims
Giant cell arteritis
Enzymes
description Objectives: Gelatinases (MMP2 and MMP9) are expressed in giant-cell arteritis (GCA) and are thought to play a role in vessel disruption. However, their activation status and enzymatic activity have not been evaluated. Our aim was to investigate the distribution and proteolytic activity of gelatinases in GCA lesions at different stages. Methods: Expression of MMP2, MMP9, MMP2-activator MMP14 and their natural inhibitors TIMP1 and TIMP2 was determined by real-time PCR and immunohistochemistry in temporal artery sections from 46 patients and 12 controls. MMP activation status and enzymatic activity were assessed by gelatin and film in situ zymography. Results: Vascular smooth muscle cells from normal specimens constitutively expressed pro-MMP2 and its inhibitor TIMP2 with no resulting proteolytic activity. In GCA MMP2, MMP9 and MMP14 were strongly expressed in their active form by infiltrating leucocytes. Inflamed arteries also expressed TIMP1 and TIMP2. However, the MMP9/TIMP1 and MMP2/TIMP2 ratios were higher in patients compared with controls, indicating an increased proteolytic balance in GCA which was confirmed by in situ zymography. Maximal gelatinase expression and activity occurred at the granulomatous areas surrounding the internal elastic lamina (IEL). Myointimal cells also expressed MMPs and exhibited proteolytic activity, suggesting a role for gelatinases in vascular remodelling and repair. Conclusions: GCA lesions show intense expression of gelatinases. Activators and inhibitors are regulated to yield enhanced gelatinase activation and proteolytic activity. Distribution of expression and proteolytic activity suggests that gelatinases have a major role not only in the progression of inflammatory infiltrates and vessel destruction but also in vessel repair.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/22456
url https://hdl.handle.net/2445/22456
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció digital del document publicat a: http://dx.doi.org/10.1136/ard.2006.068148
Annals of the Rheumatic Diseases, 2007, vol. 66, núm. 11, p. 1429-1435
http://dx.doi.org/10.1136/ard.2006.068148
dc.rights.none.fl_str_mv (c) BMJ Publishing Group Ltd, 2007
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) BMJ Publishing Group Ltd, 2007
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv BMJ Group
publisher.none.fl_str_mv BMJ Group
dc.source.none.fl_str_mv Articles publicats en revistes (Medicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301629

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