{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T20:08:03Z","timestamp":1772222883409,"version":"3.50.1"},"reference-count":31,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["23MERIT1036341"],"award-info":[{"award-number":["23MERIT1036341"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["24CDA1268148"],"award-info":[{"award-number":["24CDA1268148"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R35HL155649"],"award-info":[{"award-number":["R35HL155649"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Cilostazol, a phosphodiesterase (PDE) 3 inhibitor, and sildenafil, a PDE5 inhibitor, have been used clinically for peripheral arterial disease and erectile dysfunction or pulmonary hypertension, respectively. Recent studies report their effects on abdominal aortic aneurysm formation. However, their impacts on thoracic aortopathy remain unknown. In this study, we investigated whether cilostazol and sildenafil affect thoracic aortopathy induced by \u03b2-aminopropionitrile (BAPN) administration in mice. Bulk RNA sequencing analysis revealed that BAPN administration upregulated\n                    <jats:italic>Pde3a<\/jats:italic>\n                    transcription in the ascending aorta and\n                    <jats:italic>Pde5a<\/jats:italic>\n                    in both ascending and descending regions before thoracic aortopathy formation. Next, we tested the effects of cilostazol or sildenafil on BAPN-induced thoracic aortopathy. BAPN-administered mice were fed a diet supplemented with either cilostazol or sildenafil. Mass spectrometry measurements determined the presence of cilostazol or sildenafil in the plasma of mice fed drug-supplemented diets. However, neither drug altered BAPN-induced aortic rupture nor aneurysm formation and progression. These results provide evidence that cilostazol and sildenafil did not influence BAPN-induced thoracic aortopathy in mice.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0322434","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T17:29:30Z","timestamp":1756488570000},"page":"e0322434","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Samuel C.","family":"Tyagi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohei","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob C.","family":"Hubbuch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael K.","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Howatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-2558","authenticated-orcid":true,"given":"Hong S.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-3775","authenticated-orcid":true,"given":"Alan","family":"Daugherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-6236","authenticated-orcid":true,"given":"Hisashi","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"issue":"3","key":"pone.0322434.ref001","article-title":"Aortic aneurysms and dissections series","volume":"40","author":"YH Shen","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"pone.0322434.ref002","doi-asserted-by":"crossref","first-page":"28149","DOI":"10.1038\/srep28149","article-title":"\u03b2-Aminopropionitrile monofumarate induces thoracic aortic dissection in C57BL\/6 mice","volume":"6","author":"W Ren","year":"2016","journal-title":"Sci Rep"},{"issue":"5","key":"pone.0322434.ref003","doi-asserted-by":"crossref","DOI":"10.1152\/ajpheart.00229.2020","article-title":"Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm","volume":"320","author":"BO Aicher","year":"2021","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"6","key":"pone.0322434.ref004","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1042\/CS20171529","article-title":"Interleukin-3 stimulates matrix metalloproteinase 12 production from macrophages promoting thoracic aortic aneurysm\/dissection","volume":"132","author":"C Liu","year":"2018","journal-title":"Clin Sci (Lond)"},{"issue":"6","key":"pone.0322434.ref005","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1161\/ATVBAHA.121.315983","article-title":"Authentication of in situ measurements for thoracic aortic aneurysms in mice","volume":"41","author":"S Ohno-Urabe","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"7","key":"pone.0322434.ref006","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1161\/ATVBAHA.123.320402","article-title":"\u03b2-aminopropionitrile induces distinct pathologies in the ascending and descending thoracic aortic regions of mice","volume":"44","author":"MK Franklin","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"22","key":"pone.0322434.ref007","doi-asserted-by":"crossref","first-page":"3965","DOI":"10.1016\/0006-2952(87)90465-5","article-title":"Role of cyclic AMP- and cyclic GMP-phosphodiesterases in the control of cyclic nucleotide levels and smooth muscle tone in rat isolated aorta. 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