{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:47:00Z","timestamp":1775983620597,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,27]]},"group-title":"Pathology","reference-count":31,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Thoracic aortopathies are life-threatening diseases including aneurysm, dissection, and rupture. Phosphodiesterases (PDEs) regulate intracellular cyclic nucleotide concentrations. Recent studies report the influences of cilostazol, a PDE3 inhibitor, and sildenafil, a PDE5 inhibitor, 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":"10.1101\/2025.03.24.645113","type":"posted-content","created":{"date-parts":[[2025,3,28]],"date-time":"2025-03-28T04:04:06Z","timestamp":1743134646000},"source":"Crossref","is-referenced-by-count":1,"title":["\u03b2-aminopropionitrile-induced thoracic aortopathy is refractory to cilostazol and sildenafil in mice"],"prefix":"10.64898","author":[{"given":"Samuel C.","family":"Tyagi","sequence":"first","affiliation":[{"name":"Saha Cardiovascular Research Center, College of Medicine University of Kentucky"},{"name":"Saha Aortic Center, College of Medicine University of Kentucky"},{"name":"Department of Physiology, College of Medicine University of Kentucky"},{"name":"Department of Surgery, College of Medicine University of 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Center, College of Medicine University of Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah A.","family":"Howatt","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, College of Medicine University of Kentucky"},{"name":"Saha Aortic Center, College of Medicine University of Kentucky"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-2558","authenticated-orcid":false,"given":"Hong S.","family":"Lu","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, College of Medicine University of Kentucky"},{"name":"Saha Aortic Center, College of Medicine University of Kentucky"},{"name":"Department of Physiology, College of Medicine University of 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