{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:21:57Z","timestamp":1768508517041,"version":"3.49.0"},"posted":{"date-parts":[[2023,10,25]]},"group-title":"Pathology","reference-count":63,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>\u03b2-aminopropionitrile (BAPN) is a pharmacological inhibitor of lysyl oxidase and lysyl oxidase-like proteins. Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>BAPN was administered in drinking water for a period ranging from 1 to 12 weeks. The impacts of BAPN were first assessed with regard to dose, strain, age, and sex. BAPN-induced aortic pathological characterization was conducted using histology and immunostaining. To investigate the mechanistic basis of regional heterogeneity, ascending and descending thoracic aortas were harvested after one week of BAPN administration before the appearance of overt pathology.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>BAPN-induced aortic rupture predominantly occurred or originated in the descending thoracic aorta in young C57BL\/6J or N mice. No apparent differences were found between male and female mice. For mice surviving 12 weeks of BAPN administration, profound dilatation was consistently observed in the ascending region, while there were more heterogeneous changes in the descending thoracic region. Pathological features were distinct between the ascending and descending thoracic regions. Aortic pathology in the ascending region was characterized by luminal dilatation and elastic fiber disruption throughout the media. The descending thoracic region frequently had dissections with false lumen formation, collagen deposition, and remodeling of the wall surrounding the false lumen. Cells surrounding the false lumen were predominantly positive for \u03b1-smooth muscle actin. One week of BAPN administration compromised contractile properties in both regions equivalently, and RNA sequencing did not show obvious differences between the two aortic regions in smooth muscle cell markers, cell proliferation markers, and extracellular components.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>BAPN-induced pathologies show distinct, heterogeneous features within and between ascending and descending aortic regions in mice.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2023.10.22.563474","type":"posted-content","created":{"date-parts":[[2023,10,25]],"date-time":"2023-10-25T10:15:21Z","timestamp":1698228921000},"source":"Crossref","is-referenced-by-count":1,"title":["\u03b2-aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4993-0164","authenticated-orcid":false,"given":"Michael K.","family":"Franklin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-6236","authenticated-orcid":false,"given":"Hisashi","family":"Sawada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sohei","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0078-092X","authenticated-orcid":false,"given":"Deborah A.","family":"Howatt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5732-1951","authenticated-orcid":false,"given":"Naofumi","family":"Amioka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4984-6544","authenticated-orcid":false,"given":"Ching-Ling","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3198-9865","authenticated-orcid":false,"given":"David B.","family":"Graf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2556-6719","authenticated-orcid":false,"given":"Jessica J.","family":"Moorleghen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuriko","family":"Katsumata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-2558","authenticated-orcid":false,"given":"Hong S.","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-3775","authenticated-orcid":false,"given":"Alan","family":"Daugherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024050805583547000_2023.10.22.563474v3.1","first-page":"e37","article-title":"Aortic aneurysms and dissections series","volume":"40","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.2","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2012.1004"},{"key":"2024050805583547000_2023.10.22.563474v3.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2021.101255"},{"key":"2024050805583547000_2023.10.22.563474v3.4","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.matbio.2019.03.001","article-title":"Elastic fibers and biomechanics of the aorta: Insights from mouse studies","volume":"85-86","year":"2020","journal-title":"Matrix Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.5","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1002\/iub.2213","article-title":"Unique molecular networks: Formation and role of elastin cross-links","volume":"72","year":"2020","journal-title":"IUBMB Life"},{"key":"2024050805583547000_2023.10.22.563474v3.6","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.jvssci.2021.12.002","article-title":"Beta-Aminopropionitrile-induced aortic aneurysm and dissection in mice","volume":"3","year":"2022","journal-title":"JVS Vasc Sci"},{"key":"2024050805583547000_2023.10.22.563474v3.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.120.3122.712"},{"key":"2024050805583547000_2023.10.22.563474v3.8","first-page":"643","article-title":"Production of aortic rupture in turkey poults fed beta-aminopropionitrile","volume":"64","year":"1957","journal-title":"AMA Arch Pathol"},{"key":"2024050805583547000_2023.10.22.563474v3.9","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.140558"},{"key":"2024050805583547000_2023.10.22.563474v3.10","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00217.2012"},{"key":"2024050805583547000_2023.10.22.563474v3.11","doi-asserted-by":"publisher","DOI":"10.1042\/CS20130660"},{"key":"2024050805583547000_2023.10.22.563474v3.12","doi-asserted-by":"publisher","DOI":"10.1038\/srep28149"},{"key":"2024050805583547000_2023.10.22.563474v3.13","doi-asserted-by":"publisher","DOI":"10.7150\/thno.22467"},{"key":"2024050805583547000_2023.10.22.563474v3.14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1538\/expanim.18-0170","article-title":"Involvement of B cells in the pathophysiology of \u03b2-aminopropionitrile-induced thoracic aortic dissection in mice","volume":"68","year":"2019","journal-title":"Exp Anim"},{"key":"2024050805583547000_2023.10.22.563474v3.15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1007\/s10557-020-07005-w","article-title":"Smooth muscle sirtuin 1 blocks thoracic aortic aneurysm\/dissection development in mice","volume":"34","year":"2020","journal-title":"Cardiovasc Drugs Ther"},{"key":"2024050805583547000_2023.10.22.563474v3.16","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1631\/jzus.B2000022","article-title":"Induction of thoracic aortic dissection: a mini-review of \u03b2-aminopropionitrile-related mouse models","volume":"21","year":"2020","journal-title":"J Zhejiang Univ Sci B"},{"key":"2024050805583547000_2023.10.22.563474v3.17","first-page":"8","article-title":"The C57Bl\/6J mouse strain is more susceptible to angiotensin II-induced aortic aneurysm formation than C57Bl\/6N","volume":"318","year":"2020","journal-title":"Atherosclerosis"},{"key":"2024050805583547000_2023.10.22.563474v3.18","doi-asserted-by":"publisher","DOI":"10.3791\/59013"},{"key":"2024050805583547000_2023.10.22.563474v3.19","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","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.20","doi-asserted-by":"crossref","first-page":"339","DOI":"10.3390\/biom12020339","article-title":"Imaging techniques for aortic aneurysms and dissections in mice: comparisons of ex vivo, in situ, and ultrasound approaches","volume":"12","year":"2022","journal-title":"Biomolecules"},{"key":"2024050805583547000_2023.10.22.563474v3.21","doi-asserted-by":"publisher","DOI":"10.1002\/bimj.200810425"},{"key":"2024050805583547000_2023.10.22.563474v3.22","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp616"},{"key":"2024050805583547000_2023.10.22.563474v3.23","first-page":"100141","article-title":"clusterProfiler 4.0: A universal enrichment tool for interpreting omics data","volume":"2","year":"2021","journal-title":"Innovation (Camb"},{"key":"2024050805583547000_2023.10.22.563474v3.24","doi-asserted-by":"crossref","unstructured":"Bellini C , Bersi MR , Caulk AW , Ferruzzi J , Milewicz DM , Ramirez F , Rifkin DB , Tellides G , Yanagisawa H and Humphrey JD . Comparison of 10 murine models reveals a distinct biomechanical phenotype in thoracic aortic aneurysms. J R Soc Interface. 2017;14.","DOI":"10.1098\/rsif.2016.1036"},{"key":"2024050805583547000_2023.10.22.563474v3.25","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1007\/s10237-018-1077-9","article-title":"Local variations in material and structural properties characterize murine thoracic aortic aneurysm mechanics","volume":"18","year":"2019","journal-title":"Biomech Model Mechanobiol"},{"key":"2024050805583547000_2023.10.22.563474v3.26","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.304936"},{"key":"2024050805583547000_2023.10.22.563474v3.27","first-page":"e78","article-title":"Aortic Aneurysms and Dissections Series: Part II: Dynamic Signaling Responses in Aortic Aneurysms and Dissections","volume":"40","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.28","doi-asserted-by":"crossref","first-page":"692856","DOI":"10.3389\/fcvm.2021.692856","article-title":"The expression patterns and roles of lysyl oxidases in aortic dissection","volume":"8","year":"2021","journal-title":"Front Cardiovasc Med"},{"key":"2024050805583547000_2023.10.22.563474v3.29","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601442113"},{"key":"2024050805583547000_2023.10.22.563474v3.30","doi-asserted-by":"publisher","DOI":"10.1016\/S1570-9639(03)00053-0"},{"key":"2024050805583547000_2023.10.22.563474v3.31","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000038109.84500.1E"},{"key":"2024050805583547000_2023.10.22.563474v3.32","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-004-2340-1"},{"key":"2024050805583547000_2023.10.22.563474v3.33","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.115.307130"},{"key":"2024050805583547000_2023.10.22.563474v3.34","doi-asserted-by":"crossref","unstructured":"Li H , Guo J , Jia Y , Kong W and Li W . LOXL4 abrogation does not exaggerate angiotensin II-induced thoracic or abdominal aortic aneurysm in mice. Genes (Basel ). 2021;12.","DOI":"10.3390\/genes12040513"},{"key":"2024050805583547000_2023.10.22.563474v3.35","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.094136"},{"key":"2024050805583547000_2023.10.22.563474v3.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2018.07.001"},{"key":"2024050805583547000_2023.10.22.563474v3.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2012.09.018"},{"key":"2024050805583547000_2023.10.22.563474v3.38","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304918"},{"key":"2024050805583547000_2023.10.22.563474v3.39","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.112.300036"},{"key":"2024050805583547000_2023.10.22.563474v3.40","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1161\/HYPERTENSIONAHA.117.09822","article-title":"Vascular ADAM17 (a Disintegrin and Metalloproteinase Domain 17) is required for angiotensin II\/beta-aminopropionitrile-induced abdominal aortic aneurysm","volume":"70","year":"2017","journal-title":"Hypertension"},{"key":"2024050805583547000_2023.10.22.563474v3.41","doi-asserted-by":"crossref","first-page":"1254","DOI":"10.1161\/ATVBAHA.122.317712","article-title":"Inhibition of the renin-angiotensin system fails to suppress beta-aminopropionitrile-induced thoracic aortopathy in mice","volume":"42","year":"2022","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.42","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.11.032"},{"key":"2024050805583547000_2023.10.22.563474v3.43","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1615"},{"key":"2024050805583547000_2023.10.22.563474v3.44","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jss.2019.10.004","article-title":"Female mice exhibit abdominal aortic aneurysm protection in an established pupture model","volume":"247","year":"2020","journal-title":"J Surg Res"},{"key":"2024050805583547000_2023.10.22.563474v3.45","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.121.315715"},{"key":"2024050805583547000_2023.10.22.563474v3.46","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309524"},{"key":"2024050805583547000_2023.10.22.563474v3.47","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1038\/s41598-021-04089-8","article-title":"Experimental aortic aneurysm severity and growth depend on topical elastase concentration and lysyl oxidase inhibition","volume":"12","year":"2022","journal-title":"Sci Rep"},{"key":"2024050805583547000_2023.10.22.563474v3.48","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1111\/j.1749-6632.1968.tb53822.x","article-title":"A combined quantitative chemical, light, and electron microscope study of aortic development in normal and nitrile-treated mice. Possible implications for elucidating nitrile-induced aortic lesions and regarding the genesis of spontaneous arterial lesions","volume":"149","year":"1968","journal-title":"Ann N Y Acad Sci"},{"key":"2024050805583547000_2023.10.22.563474v3.49","first-page":"e14631","article-title":"A validated mouse model capable of recapitulating the protective effects of female sex hormones on ascending aortic aneurysms and dissections (AADs)","volume":"8","year":"2020","journal-title":"Physiol Rep"},{"key":"2024050805583547000_2023.10.22.563474v3.50","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1161\/ATVBAHA.119.313336","article-title":"High salt intake worsens aortic dissection in mice: involvement of IL (interleukin)-17A-dependent ECM (extracellular matrix) metabolism","volume":"40","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2024050805583547000_2023.10.22.563474v3.51","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-016-1028-3"},{"issue":"Suppl 2","key":"2024050805583547000_2023.10.22.563474v3.52","first-page":"739","article-title":"Clinical care of adult Turner syndrome--new aspects","volume":"9","year":"2012","journal-title":"Pediatr Endocrinol Rev"},{"key":"2024050805583547000_2023.10.22.563474v3.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jvs.2016.06.120"},{"key":"2024050805583547000_2023.10.22.563474v3.54","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M412501200"},{"key":"2024050805583547000_2023.10.22.563474v3.55","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1002\/dvdy.283","article-title":"Developmental origins of mechanical homeostasis in the aorta","volume":"250","year":"2021","journal-title":"Dev Dyn"},{"key":"2024050805583547000_2023.10.22.563474v3.56","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.212837"},{"key":"2024050805583547000_2023.10.22.563474v3.57","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.141069"},{"key":"2024050805583547000_2023.10.22.563474v3.58","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.309599"},{"key":"2024050805583547000_2023.10.22.563474v3.59","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1161\/CIRCULATIONAHA.121.058173","article-title":"Second heart field-derived cells contribute to angiotensin II-mediated ascending aortopathies","volume":"145","year":"2022","journal-title":"Circulation"},{"key":"2024050805583547000_2023.10.22.563474v3.60","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.309322"},{"key":"2024050805583547000_2023.10.22.563474v3.61","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.actbio.2021.07.059","article-title":"Biomechanical consequences of compromised elastic fiber integrity and matrix cross-linking on abdominal aortic aneurysmal enlargement","volume":"134","year":"2021","journal-title":"Acta Biomater"},{"key":"2024050805583547000_2023.10.22.563474v3.62","doi-asserted-by":"publisher","DOI":"10.1007\/s10439-013-0799-1"},{"key":"2024050805583547000_2023.10.22.563474v3.63","first-page":"0310081","article-title":"Fundamental Roles of Axial Stretch in Isometric and Isobaric Evaluations of Vascular Contractility","volume":"141","year":"2019","journal-title":"J Biomech Eng"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.10.22.563474","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:25:46Z","timestamp":1768454746000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2023.10.22.563474"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,25]]},"references-count":63,"URL":"https:\/\/doi.org\/10.1101\/2023.10.22.563474","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1161\/ATVBAHA.123.320402","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2023,10,25]]},"subtype":"preprint"}}