Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice

Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has be...

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Autores: Varona, Saray|||0000-0002-7375-313X, Puertas Umbert, Lídia|||0000-0002-2739-6522, Galán, María|||0000-0002-4758-8388, Orriols, Mar, Cañes Esteve, Laia|||0000-0002-9579-1321, Aguiló, Silvia|||0000-0003-0672-8388, Camacho, Mercedes|||0000-0001-5970-3294, Sirvent, M., Andrés, Vicente|||0000-0002-0125-7209, Martínez-González, José|||0000-0002-3894-7166, Rodríguez, Cristina|||0000-0002-6472-5647
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:269922
Acceso en línea:https://ddd.uab.cat/record/269922
https://dx.doi.org/urn:doi:10.3390/antiox10030460
Access Level:acceso abierto
Palabra clave:Abdominal aortic aneurysm
Reactive oxygen species
PDE4B
Rolipram
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spelling Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in micepde4b as a target in AAAVarona, Saray|||0000-0002-7375-313XPuertas Umbert, Lídia|||0000-0002-2739-6522Galán, María|||0000-0002-4758-8388Orriols, MarCañes Esteve, Laia|||0000-0002-9579-1321Aguiló, Silvia|||0000-0003-0672-8388Camacho, Mercedes|||0000-0001-5970-3294Sirvent, M.Andrés, Vicente|||0000-0002-0125-7209Martínez-González, José|||0000-0002-3894-7166Rodríguez, Cristina|||0000-0002-6472-5647Abdominal aortic aneurysmReactive oxygen speciesPDE4BRolipramAbdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Here, we used angiotensin II (AngII)-infused apolipoprotein E deficient mice to study the involvement of the PDE4 subfamily in aneurysmal disease. PDE4B but not PDE4D was upregulated in inflammatory cells from both experimental and human AAA. The administration of the PDE4 selective inhibitor rolipram (3 mg/kg/day) to AngII-challenged mice (1000 ng/kg bodyweight/min) protected against AAA formation, limiting the progressive increase in the aortic diameter without affecting the blood pressure. The drug strongly attenuated the rise in vascular oxidative stress (superoxide anion) induced by AngII, and decreased the expression of inflammatory markers, as well as the recruitment of macrophages (MAC3+), lymphocytes (CD3+), and neutrophils (ELANE+) into the vessel wall. Rolipram also normalized the vascular MMP2 expression and MMP activity, preserving the elastin integrity and improving the vascular remodelling. These results point to PDE4B as a new therapeutic target for AAA. 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/269922https://dx.doi.org/urn:doi:10.3390/antiox10030460reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengAgència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-00333Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/0919Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PID2019-108489RB-100Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RTI2018-094727-B-100open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2699222026-06-06T12:50:31Z
dc.title.none.fl_str_mv Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
pde4b as a target in AAA
title Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
spellingShingle Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
Varona, Saray|||0000-0002-7375-313X
Abdominal aortic aneurysm
Reactive oxygen species
PDE4B
Rolipram
title_short Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
title_full Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
title_fullStr Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
title_full_unstemmed Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
title_sort Rolipram prevents the formation of abdominal aortic aneurysm (Aaa) in mice
dc.creator.none.fl_str_mv Varona, Saray|||0000-0002-7375-313X
Puertas Umbert, Lídia|||0000-0002-2739-6522
Galán, María|||0000-0002-4758-8388
Orriols, Mar
Cañes Esteve, Laia|||0000-0002-9579-1321
Aguiló, Silvia|||0000-0003-0672-8388
Camacho, Mercedes|||0000-0001-5970-3294
Sirvent, M.
Andrés, Vicente|||0000-0002-0125-7209
Martínez-González, José|||0000-0002-3894-7166
Rodríguez, Cristina|||0000-0002-6472-5647
author Varona, Saray|||0000-0002-7375-313X
author_facet Varona, Saray|||0000-0002-7375-313X
Puertas Umbert, Lídia|||0000-0002-2739-6522
Galán, María|||0000-0002-4758-8388
Orriols, Mar
Cañes Esteve, Laia|||0000-0002-9579-1321
Aguiló, Silvia|||0000-0003-0672-8388
Camacho, Mercedes|||0000-0001-5970-3294
Sirvent, M.
Andrés, Vicente|||0000-0002-0125-7209
Martínez-González, José|||0000-0002-3894-7166
Rodríguez, Cristina|||0000-0002-6472-5647
author_role author
author2 Puertas Umbert, Lídia|||0000-0002-2739-6522
Galán, María|||0000-0002-4758-8388
Orriols, Mar
Cañes Esteve, Laia|||0000-0002-9579-1321
Aguiló, Silvia|||0000-0003-0672-8388
Camacho, Mercedes|||0000-0001-5970-3294
Sirvent, M.
Andrés, Vicente|||0000-0002-0125-7209
Martínez-González, José|||0000-0002-3894-7166
Rodríguez, Cristina|||0000-0002-6472-5647
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Abdominal aortic aneurysm
Reactive oxygen species
PDE4B
Rolipram
topic Abdominal aortic aneurysm
Reactive oxygen species
PDE4B
Rolipram
description Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Here, we used angiotensin II (AngII)-infused apolipoprotein E deficient mice to study the involvement of the PDE4 subfamily in aneurysmal disease. PDE4B but not PDE4D was upregulated in inflammatory cells from both experimental and human AAA. The administration of the PDE4 selective inhibitor rolipram (3 mg/kg/day) to AngII-challenged mice (1000 ng/kg bodyweight/min) protected against AAA formation, limiting the progressive increase in the aortic diameter without affecting the blood pressure. The drug strongly attenuated the rise in vascular oxidative stress (superoxide anion) induced by AngII, and decreased the expression of inflammatory markers, as well as the recruitment of macrophages (MAC3+), lymphocytes (CD3+), and neutrophils (ELANE+) into the vessel wall. Rolipram also normalized the vascular MMP2 expression and MMP activity, preserving the elastin integrity and improving the vascular remodelling. These results point to PDE4B as a new therapeutic target for AAA.
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/269922
https://dx.doi.org/urn:doi:10.3390/antiox10030460
url https://ddd.uab.cat/record/269922
https://dx.doi.org/urn:doi:10.3390/antiox10030460
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-00333
Instituto de Salud Carlos III https://doi.org/10.13039/501100004587 PI18/0919
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 PID2019-108489RB-100
Ministerio de Ciencia e Innovación https://doi.org/10.13039/501100004837 RTI2018-094727-B-100
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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