{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:50:57Z","timestamp":1785750657119,"version":"3.56.0"},"reference-count":15,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,1,18]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">cGMP\u2010hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP\u2010dependent protein kinase I (PKGI)\u2013dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">AAA was induced in C57BL\/6J male mice by periaortic elastase in combination with blocking elastin\/collagen formation via 3\u2010aminopropionitrile fumarate salt for 35\u00a0days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre\u2010existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.121.023053","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T13:03:51Z","timestamp":1641387831000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":22,"title":["Sildenafil (Viagra) Aggravates the Development of Experimental Abdominal Aortic Aneurysm"],"prefix":"10.1161","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7833-5172","authenticated-orcid":false,"given":"Chongyang","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Medicine and Dentistry Aab Cardiovascular Research InstituteUniversity of Rochester Rochester NY"},{"name":"Department of Pharmacology and Physiology School of Medicine and Dentistry University of Rochester Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Mohan","sequence":"additional","affiliation":[{"name":"School of Medicine and Dentistry Aab Cardiovascular Research InstituteUniversity of Rochester Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6269-742X","authenticated-orcid":false,"given":"Hangchuan","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Clinical &amp; Translational Research University of Rochester Medical Center Rochester NY"},{"name":"Department of Public Health Sciences University of Rochester Medical Center Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1397-6358","authenticated-orcid":false,"given":"Chen","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Medicine and Dentistry Aab Cardiovascular Research InstituteUniversity of Rochester Rochester NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.2310\/6670.2008.00085"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.114.000943"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/hgv.2015.28"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1124\/pr.110.002907"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0090-4295(02)01686-2"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-5347(01)63100-8"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2013.06.019"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.smj.0000240732.65859.aa"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2011.07.016"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1510\/icvts.2009.205849"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48432-6"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20201057"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414364111"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43322-3"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00028.2009"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.121.023053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T11:21:48Z","timestamp":1715599308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.121.023053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,18]]},"references-count":15,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,1,18]]}},"alternative-id":["10.1161\/JAHA.121.023053"],"URL":"https:\/\/doi.org\/10.1161\/jaha.121.023053","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,18]]},"assertion":[{"value":"2021-06-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e023053"}}