{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:04:51Z","timestamp":1789617891477,"version":"build-2803163510"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T00:00:00Z","timestamp":1615852800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI18\/0919"],"award-info":[{"award-number":["PI18\/0919"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["RTI2018-094727-B-100"],"award-info":[{"award-number":["RTI2018-094727-B-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"publisher","award":["PID2019-108489RB-100"],"award-info":[{"award-number":["PID2019-108489RB-100"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ag\u00e8ncia de Gesti\u00f3 d'Ajuts Universitaris i de Recerca (AGAUR)","award":["2017-SGR-00333"],"award-info":[{"award-number":["2017-SGR-00333"]}]},{"name":"Sociedad Espa\u00f1ola de Arteriosclerosis","award":["Beca FEA 2020 Investigaci\u00f3n B\u00e1sica"],"award-info":[{"award-number":["Beca FEA 2020 Investigaci\u00f3n B\u00e1sica"]}]},{"name":"Sociedad Espa\u00f1ola de Cardiologia","award":["SEC\/FEC-INV-BAS 20\/005"],"award-info":[{"award-number":["SEC\/FEC-INV-BAS 20\/005"]}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/antiox10030460","type":"journal-article","created":{"date-parts":[[2021,3,16]],"date-time":"2021-03-16T02:50:58Z","timestamp":1615863058000},"page":"460","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA"],"prefix":"10.3390","volume":"10","author":[{"given":"Saray","family":"Varona","sequence":"first","affiliation":[{"name":"Departmento de Patolog\u00eda Experimental, Instituto de Investigaciones Biom\u00e9dicas de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), 08036 Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Puertas","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4758-8388","authenticated-orcid":false,"given":"Mar\u00eda","family":"Gal\u00e1n","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar","family":"Orriols","sequence":"additional","affiliation":[{"name":"Departmento de Patolog\u00eda Experimental, Instituto de Investigaciones Biom\u00e9dicas de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), 08036 Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Ca\u00f1es","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Aguil\u00f3","sequence":"additional","affiliation":[{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5970-3294","authenticated-orcid":false,"given":"Mercedes","family":"Camacho","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5912-8760","authenticated-orcid":false,"given":"Marc","family":"Sirvent","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Angiology and Vascular Surgery Service, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0125-7209","authenticated-orcid":false,"given":"Vicente","family":"Andr\u00e9s","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Vascular Pathophysiology Area, Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3894-7166","authenticated-orcid":false,"given":"Jos\u00e9","family":"Mart\u00ednez-Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Departmento de Patolog\u00eda Experimental, Instituto de Investigaciones Biom\u00e9dicas de Barcelona-Consejo Superior de Investigaciones Cient\u00edficas (IIBB-CSIC), 08036 Barcelona, Spain"},{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6472-5647","authenticated-orcid":false,"given":"Cristina","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Instituto de Investigaci\u00f3n Biom\u00e9dica Sant Pau, 08041 Barcelona, Spain"},{"name":"Regulatory Mechanisms of Cardiovascular Remodelling Group, Institut de Recerca Hospital de la Santa Creu i Sant Pau (IRHSCSP), 08025 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nrcardio.2010.180","article-title":"Pathophysiology and epidemiology of abdominal aortic aneurysms","volume":"8","author":"Nordon","year":"2011","journal-title":"Nat. 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