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Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA

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 principales: Varona, Saray, Puertas, Lídia, Galán, María, Orriols, Mar, Cañes, Laia, Aguiló, Silvia, Camacho, Mercedes, Sirvent, Marc, Andrés, Vicente, Martínez-González, José, Rodríguez, Cristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000788/
https://www.ncbi.nlm.nih.gov/pubmed/33809405
http://dx.doi.org/10.3390/antiox10030460
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author Varona, Saray
Puertas, Lídia
Galán, María
Orriols, Mar
Cañes, Laia
Aguiló, Silvia
Camacho, Mercedes
Sirvent, Marc
Andrés, Vicente
Martínez-González, José
Rodríguez, Cristina
author_facet Varona, Saray
Puertas, Lídia
Galán, María
Orriols, Mar
Cañes, Laia
Aguiló, Silvia
Camacho, Mercedes
Sirvent, Marc
Andrés, Vicente
Martínez-González, José
Rodríguez, Cristina
author_sort Varona, Saray
collection PubMed
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.
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spelling pubmed-80007882021-03-28 Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA Varona, Saray Puertas, Lídia Galán, María Orriols, Mar Cañes, Laia Aguiló, Silvia Camacho, Mercedes Sirvent, Marc Andrés, Vicente Martínez-González, José Rodríguez, Cristina Antioxidants (Basel) Article 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. MDPI 2021-03-16 /pmc/articles/PMC8000788/ /pubmed/33809405 http://dx.doi.org/10.3390/antiox10030460 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Varona, Saray
Puertas, Lídia
Galán, María
Orriols, Mar
Cañes, Laia
Aguiló, Silvia
Camacho, Mercedes
Sirvent, Marc
Andrés, Vicente
Martínez-González, José
Rodríguez, Cristina
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: PDE4B as a Target in AAA
title_full Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA
title_fullStr Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA
title_full_unstemmed Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA
title_short Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA
title_sort rolipram prevents the formation of abdominal aortic aneurysm (aaa) in mice: pde4b as a target in aaa
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000788/
https://www.ncbi.nlm.nih.gov/pubmed/33809405
http://dx.doi.org/10.3390/antiox10030460
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