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This work was supported by Instituto de Salud Carlos III (ISCIII) [PI18/0919], the Spanish Ministerio de Ciencia e Innovacion (MICINN) [RTI2018-094727-B-100 and PID2019-108489RB-100], the Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [2017-SGR-00333], Sociedad Espanola de Arteriosclerosis [Beca FEA 2020 Investigacion Basica], and Sociedad Espanola de Cardiologia [SEC/FEC-INV-BAS 20/005]. The study was co-founded by Fondo Europeo de Desarrollo Regional (FEDER), "A way to make Europe". L.C. was supported by a FI (AGAUR). The CNIC is supported by MICINN, ISCIII, and the Pro-CNIC Foundation.

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Galan, MariaAuthor
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Article

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

Publicated to:Antioxidants. 10 (3): 460-17 - 2021-03-01 10(3), DOI: 10.3390/antiox10030460

Authors: Varona, Saray; Puertas, Lidia; Galan, Maria; Orriols, Mar; Canes, Laia; Aguilo, Silvia; Camacho, Mercedes; Sirvent, Marc; Andres, Vicente; Martinez-Gonzalez, Jose; Rodriguez, Cristina

Affiliations

CIBER Enfermedades Cardiovasc, ISCIII, Madrid 28029, Spain - Author
Ctr Nacl Invest Cardiovasc Carlos III CNIC, Vasc Pathophysiol Area, Madrid 28029, Spain - Author
Hosp Badalona Germans Trias & Pujol, Angiol & Vasc Surg Serv, Badalona 08916, Spain - Author
Inst Invest Biomed Barcelona, Dept Patol Expt, Consejo Super Invest Cient IIBB CSIC, Barcelona 08036, Spain - Author
Inst Invest Biomed St Pau, Regulatory Mech Cardiovasc Remodelling Grp, Barcelona 08041, Spain - Author
Inst Recerca Hosp Santa Creu & St Pau IRHSCSP, Regulatory Mech Cardiovasc Remodelling Grp, Barcelona 08025, Spain - Author
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Abstract

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.

Keywords
Abdominal aortic aneurysmCellsCyclic-nucleotide phosphodiesterasesEnzymesGene-expressionInflammationInhibitorsMoleculesOxidative stressPathogenesisPde4bReactive oxygen speciesRoflumilastRolipram

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Antioxidants due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2021, it was in position 4/63, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Medicinal. Notably, the journal is positioned above the 90th percentile.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.16. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 14, 2024)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.24 (source consulted: FECYT Feb 2024)
  • Field Citation Ratio (FCR) from Dimensions: 3.61 (source consulted: Dimensions May 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2025-05-02, the following number of citations:

  • WoS: 13
  • Scopus: 14
  • Europe PMC: 9
  • OpenCitations: 10
Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-05-02:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 19.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 19 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 17.7.
  • The number of mentions on the social network X (formerly Twitter): 6 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.