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Article

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

1
Departmento de Patología Experimental, Instituto de Investigaciones Biomédicas de Barcelona-Consejo Superior de Investigaciones Científicas (IIBB-CSIC), 08036 Barcelona, Spain
2
CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain
3
Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigación Biomédica Sant Pau, 08041 Barcelona, Spain
4
Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain
5
Angiology and Vascular Surgery Service, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain
6
Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally.
Academic Editor: Guillermo Zalba
Antioxidants 2021, 10(3), 460; https://doi.org/10.3390/antiox10030460
Received: 18 February 2021 / Revised: 10 March 2021 / Accepted: 11 March 2021 / Published: 16 March 2021
(This article belongs to the Special Issue Oxidative Stress in Vascular Pathophysiology)
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. View Full-Text
Keywords: abdominal aortic aneurysm; reactive oxygen species; PDE4B; rolipram abdominal aortic aneurysm; reactive oxygen species; PDE4B; rolipram
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MDPI and ACS Style

Varona, S.; Puertas, L.; Galán, M.; Orriols, M.; Cañes, L.; Aguiló, S.; Camacho, M.; Sirvent, M.; Andrés, V.; Martínez-González, J.; Rodríguez, C. Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA. Antioxidants 2021, 10, 460. https://doi.org/10.3390/antiox10030460

AMA Style

Varona S, Puertas L, Galán M, Orriols M, Cañes L, Aguiló S, Camacho M, Sirvent M, Andrés V, Martínez-González J, Rodríguez C. Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA. Antioxidants. 2021; 10(3):460. https://doi.org/10.3390/antiox10030460

Chicago/Turabian Style

Varona, Saray, Lídia Puertas, María Galán, Mar Orriols, Laia Cañes, Silvia Aguiló, Mercedes Camacho, Marc Sirvent, Vicente Andrés, José Martínez-González, and Cristina Rodríguez. 2021. "Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA" Antioxidants 10, no. 3: 460. https://doi.org/10.3390/antiox10030460

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