{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T14:43:10Z","timestamp":1769524990823,"version":"3.49.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":31,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"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\/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"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-33367-y","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T08:35:07Z","timestamp":1766738107000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Metformin does not attenuate angiotensin II-induced aortic aneurysms in low-density lipoprotein receptor deficient mice"],"prefix":"10.1038","volume":"16","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"}]},{"given":"Hong S.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Daugherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hisashi","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"33367_CR1","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1093\/aje\/154.3.236","volume":"154","author":"K Singh","year":"2001","unstructured":"Singh, K., B\u00f8naa, K. H., Jacobsen, B. K., Bj\u00f8rk, L. & Solberg, S. Prevalence of and risk factors for abdominal aortic aneurysms in a population-based study: The Troms\u00f8 Study. Am. J. Epidemiol. 154, 236\u2013244. https:\/\/doi.org\/10.1093\/aje\/154.3.236 (2001).","journal-title":"Am. J. Epidemiol."},{"key":"33367_CR2","doi-asserted-by":"publisher","first-page":"1895","DOI":"10.1056\/NEJMcp012641","volume":"348","author":"JT Powell","year":"2003","unstructured":"Powell, J. T. & Greenhalgh, R. M. Clinical practice. Small abdominal aortic aneurysms. N Engl. J. Med. 348, 1895\u20131901. https:\/\/doi.org\/10.1056\/NEJMcp012641 (2003).","journal-title":"N Engl. J. Med."},{"key":"33367_CR3","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1067\/mva.2002.125479","volume":"36","author":"M Heikkinen","year":"2002","unstructured":"Heikkinen, M., Salenius, J. P. & Auvinen, O. Ruptured abdominal aortic aneurysm in a well-defined geographic area. J. Vasc Surg. 36, 291\u2013296. https:\/\/doi.org\/10.1067\/mva.2002.125479 (2002).","journal-title":"J. Vasc Surg."},{"key":"33367_CR4","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.jvs.2017.10.044","volume":"67","author":"EL Chaikof","year":"2018","unstructured":"Chaikof, E. L. et al. The society for vascular surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J. Vasc Surg. 67, 2\u201377e72. https:\/\/doi.org\/10.1016\/j.jvs.2017.10.044 (2018).","journal-title":"J. Vasc Surg."},{"key":"33367_CR5","doi-asserted-by":"publisher","first-page":"2459","DOI":"10.1161\/circulationaha.116.022194","volume":"133","author":"CC Low Wang","year":"2016","unstructured":"Low Wang, C. C., Hess, C. N., Hiatt, W. R. & Goldfine, A. B. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus - mechanisms, management, and clinical considerations. Circulation 133, 2459\u20132502. https:\/\/doi.org\/10.1161\/circulationaha.116.022194 (2016).","journal-title":"Circulation"},{"key":"33367_CR6","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1161\/circulationaha.120.046464","volume":"144","author":"L Edgar","year":"2021","unstructured":"Edgar, L. et al. Hyperglycemia induces trained immunity in macrophages and their precursors and promotes atherosclerosis. Circulation 144, 961\u2013982. https:\/\/doi.org\/10.1161\/circulationaha.120.046464 (2021).","journal-title":"Circulation"},{"key":"33367_CR7","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.2337\/dc13-2432","volume":"37","author":"B Shah","year":"2014","unstructured":"Shah, B. et al. Diabetes and vascular disease in different arterial territories. Diabetes Care. 37, 1636\u20131642. https:\/\/doi.org\/10.2337\/dc13-2432 (2014).","journal-title":"Diabetes Care"},{"key":"33367_CR8","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.ejvs.2013.12.007","volume":"47","author":"P De Rango","year":"2014","unstructured":"De Rango, P., Farchioni, L., Fiorucci, B. & Lenti, M. Diabetes and abdominal aortic aneurysms. Eur. J. Vasc Endovasc Surg. 47, 243\u2013261. https:\/\/doi.org\/10.1016\/j.ejvs.2013.12.007 (2014).","journal-title":"Eur. J. Vasc Endovasc Surg."},{"key":"33367_CR9","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1177\/0003319715602414","volume":"67","author":"H Takagi","year":"2016","unstructured":"Takagi, H. & Umemoto, T. Diabetes and abdominal aortic aneurysm growth. Angiology 67, 513\u2013525. https:\/\/doi.org\/10.1177\/0003319715602414 (2016).","journal-title":"Angiology"},{"key":"33367_CR10","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jvs.2016.02.020","volume":"64","author":"N Fujimura","year":"2016","unstructured":"Fujimura, N. et al. Metformin treatment status and abdominal aortic aneurysm disease progression. J. Vasc Surg. 64, 46\u201354e48. https:\/\/doi.org\/10.1016\/j.jvs.2016.02.020 (2016).","journal-title":"J. Vasc Surg."},{"key":"33367_CR11","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1136\/heartjnl-2018-314639","volume":"105","author":"X Yu","year":"2019","unstructured":"Yu, X. et al. Metformin prescription and aortic aneurysm: systematic review and meta-analysis. Heart 105, 1351\u20131357. https:\/\/doi.org\/10.1136\/heartjnl-2018-314639 (2019).","journal-title":"Heart"},{"key":"33367_CR12","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1016\/j.jvs.2018.06.194","volume":"69","author":"NK Itoga","year":"2019","unstructured":"Itoga, N. K. et al. Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. Veteran population. J. Vasc Surg. 69, 710\u2013716e713. https:\/\/doi.org\/10.1016\/j.jvs.2018.06.194 (2019).","journal-title":"J. Vasc Surg."},{"key":"33367_CR13","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13578-019-0332-9","volume":"9","author":"Z Wang","year":"2019","unstructured":"Wang, Z. et al. Metformin represses the pathophysiology of AAA by suppressing the activation of PI3K\/AKT\/mTOR\/autophagy pathway in ApoE(-\/-) mice. Cell. Biosci. 9, 68. https:\/\/doi.org\/10.1186\/s13578-019-0332-9 (2019).","journal-title":"Cell. Biosci."},{"key":"33367_CR14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.jvssci.2020.11.031","volume":"2","author":"A Kunath","year":"2021","unstructured":"Kunath, A. et al. Inhibition of angiotensin-induced aortic aneurysm by metformin in apolipoprotein E-deficient mice. JVS Vasc Sci. 2, 33\u201342. https:\/\/doi.org\/10.1016\/j.jvssci.2020.11.031 (2021).","journal-title":"JVS Vasc Sci."},{"key":"33367_CR15","doi-asserted-by":"publisher","first-page":"1605","DOI":"10.1172\/JCI7818","volume":"105","author":"A Daugherty","year":"2000","unstructured":"Daugherty, A., Manning, M. W. & Cassis, L. A. Angiotensin II promotes atherosclerotic lesions and aneurysms in apolipoprotein E-deficient mice. J. Clin. Invest. 105, 1605\u20131612 (2000).","journal-title":"J. Clin. Invest."},{"key":"33367_CR16","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1161\/ATVBAHA.121.317058","volume":"42","author":"H Sawada","year":"2022","unstructured":"Sawada, H., Lu, H. S., Cassis, L. A. & Daugherty, A. Twenty years of studying AngII (angiotensin II)-induced abdominal aortic pathologies in mice: continuing questions and challenges to provide insight into the human disease. Arterioscler. Thromb. Vasc Biol. 42, 277\u2013288. https:\/\/doi.org\/10.1161\/ATVBAHA.121.317058 (2022).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"33367_CR17","doi-asserted-by":"publisher","first-page":"1826","DOI":"10.1161\/ATVBAHA.115.305482","volume":"35","author":"J Liu","year":"2015","unstructured":"Liu, J. et al. Associations of ApoAI and apoB-containing lipoproteins with AngII-induced abdominal aortic aneurysms in mice. Arterioscler. Thromb. Vasc Biol. 35, 1826\u20131834 (2015).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"33367_CR18","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1161\/01.ATV.0000118013.72016.ea","volume":"24","author":"A Daugherty","year":"2004","unstructured":"Daugherty, A. & Cassis, L. A. Mouse models of abdominal aortic aneurysms. Arterioscler. Thromb. Vasc Biol. 24, 429\u2013434 (2004).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"33367_CR19","doi-asserted-by":"publisher","first-page":"1734","DOI":"10.1161\/ATVBAHA.116.306874","volume":"36","author":"GS Getz","year":"2016","unstructured":"Getz, G. S. & Reardon, C. A. Do the Apoe-\/- and Ldlr-\/- mice yield the same insight on atherogenesis? Arterioscler. Thromb. Vasc Biol. 36, 1734\u20131741 (2016).","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"33367_CR20","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.cell.2015.01.036","volume":"161","author":"JL Goldstein","year":"2015","unstructured":"Goldstein, J. L. & Brown, M. S. A century of cholesterol and coronaries: from plaques to genes to statins. Cell 161, 161\u2013172. https:\/\/doi.org\/10.1016\/j.cell.2015.01.036 (2015).","journal-title":"Cell"},{"key":"33367_CR21","doi-asserted-by":"publisher","first-page":"E207","DOI":"10.1152\/ajpendo.2002.282.1.E207","volume":"282","author":"SA Schreyer","year":"2002","unstructured":"Schreyer, S. A., Vick, C., Lystig, T. C., Mystkowski, P. & LeBoeuf, R. C. LDL receptor but not apolipoprotein E deficiency increases diet-induced obesity and diabetes in mice. Am. J. Physiol. Endo Metab. 282, E207\u2013E214 (2002).","journal-title":"Am. J. Physiol. Endo Metab."},{"key":"33367_CR22","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1161\/CIRCULATIONAHA.121.058173","volume":"145","author":"H Sawada","year":"2022","unstructured":"Sawada, H. et al. Second heart field-derived cells contribute to angiotensin II-mediated ascending aortopathies. Circulation 145, 987\u20131001. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.121.058173 (2022).","journal-title":"Circulation"},{"key":"33367_CR23","doi-asserted-by":"publisher","first-page":"975","DOI":"10.1016\/j.jvs.2010.05.086","volume":"52","author":"N Miyama","year":"2010","unstructured":"Miyama, N. et al. Hyperglycemia limits experimental aortic aneurysm progression. J. Vasc Surg. 52, 975\u2013983 (2010).","journal-title":"J. Vasc Surg."},{"key":"33367_CR24","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1146\/annurev.genom.1.1.507","volume":"1","author":"RW Mahley","year":"2000","unstructured":"Mahley, R. W. & Rall, S. C. J. Apolipoproteine: Far more than a lipid transport protein. Annu. Rev. Genomics Hum. Genet. 1, 507\u2013537 (2000).","journal-title":"Annu. Rev. Genomics Hum. Genet."},{"key":"33367_CR25","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1023\/a:1020884312053","volume":"32","author":"AA Bachmanov","year":"2002","unstructured":"Bachmanov, A. A., Reed, D. R., Beauchamp, G. K. & Tordoff, M. G. Food intake, water intake, and drinking spout side preference of 28 mouse strains. Behav. Genet. 32, 435\u2013443. https:\/\/doi.org\/10.1023\/a:1020884312053 (2002).","journal-title":"Behav. Genet."},{"key":"33367_CR26","doi-asserted-by":"publisher","first-page":"100102","DOI":"10.1016\/j.jvssci.2023.100102","volume":"4","author":"B Xu","year":"2023","unstructured":"Xu, B. et al. Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms. JVS Vasc Sci. 4, 100102. https:\/\/doi.org\/10.1016\/j.jvssci.2023.100102 (2023).","journal-title":"JVS Vasc Sci."},{"key":"33367_CR27","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1038\/s41586-019-1911-y","volume":"578","author":"AP Coll","year":"2020","unstructured":"Coll, A. P. et al. GDF15 mediates the effects of metformin on body weight and energy balance. Nature 578, 444\u2013448. https:\/\/doi.org\/10.1038\/s41586-019-1911-y (2020).","journal-title":"Nature"},{"key":"33367_CR28","doi-asserted-by":"publisher","first-page":"441","DOI":"10.7326\/0003-4819-126-6-199703150-00004","volume":"126","author":"FA Lederle","year":"1997","unstructured":"Lederle, F. A. et al. Prevalence and associations of abdominal aortic aneurysm detected through screening. Aneurysm detection and management (ADAM) veterans affairs cooperative study group. Ann. Intern. Med. 126, 441\u2013449 (1997).","journal-title":"Ann. Intern. Med."},{"key":"33367_CR29","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.ejvs.2011.12.026","volume":"43","author":"FA Lederle","year":"2012","unstructured":"Lederle, F. A. The strange relationship between diabetes and abdominal aortic aneurysm. Eur. J. Vasc Endovasc Surg. 43, 254\u2013256 (2012).","journal-title":"Eur. J. Vasc Endovasc Surg."},{"key":"33367_CR30","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.ejvs.2025.04.052","volume":"70","author":"W. Eilenberg","year":"2025","unstructured":"Eilenberg, W. et al. Editor's Choice Metformin to Inhibit Progression of Abdominal Aortic Aneurysm: A Randomised, Placebo Controlled Clinical Trial. Eur. J. Vasc. Endovasc. Surg. 70, 417\u2013425 (2025).","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"33367_CR31","first-page":"e53191","volume":"103","author":"H Lu","year":"2015","unstructured":"Lu, H. et al. Subcutaneous angiotensin II infusion using osmotic pumps induces aortic aneurysms in mice. JoVE 103, e53191 (2015).","journal-title":"JoVE"},{"key":"33367_CR32","doi-asserted-by":"publisher","first-page":"e0153811","DOI":"10.1371\/journal.pone.0153811","volume":"11","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. TGF-beta neutralization enhances AngII-induced aortic rupture and aneurysm in both thoracic and abdominal regions. PLoS One. 11, e0153811 (2016).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33367-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33367-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33367-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T02:02:18Z","timestamp":1769479338000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-33367-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["33367"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-33367-y","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]},"assertion":[{"value":"26 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3395"}}