{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:50:45Z","timestamp":1787010645758,"version":"build-2736575974"},"posted":{"date-parts":[[2025,11,30]]},"group-title":"Pathology","reference-count":30,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T00:00:00Z","timestamp":1764460800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["R35HL155649"],"award-info":[{"award-number":["R35HL155649"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"crossref","award":["K01HL149984"],"award-info":[{"award-number":["K01HL149984"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"crossref","award":["23MERIT1036341"],"award-info":[{"award-number":["23MERIT1036341"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"crossref","award":["22CVD03"],"award-info":[{"award-number":["22CVD03"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,3,25]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Mice harboring a missense variant (C1041G) of\n                    <jats:italic>fibrillin-1<\/jats:italic>\n                    (\n                    <jats:italic>Fbn1<\/jats:italic>\n                    ) have been used extensively for aortopathy research, but do not mimic all facets of the human disease. The role of increased angiotensin II (AngII) or blood pressure in determining the arterial phenotype of these mice remains incompletely defined. The purpose of this study was to determine whether AngII, either directly or indirectly through increased blood pressure, promotes pathology in the proximal thoracic aorta and beyond.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>+\/+<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>and Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    littermates were infused with either AngII or norepinephrine (NE) via subcutaneously implanted osmotic pumps. Micro computed tomography (microCT) was used to visualize vascular pathologies. Maximal arterial dimensions were measured using in situ or microCT images.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    AngII infusion dramatically augmented aortopathy in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice. Aortic dissection was visible within 3 days of AngII infusion. Over 50% of male\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice died during AngII infusion, primarily due to aortic rupture in either the thoracic or abdominal regions. Surviving males had increased ascending and suprarenal aortic diameters and developed pathological lesions at the celiac and superior mesenteric branches of the abdominal aorta. Female mice had a much lower incidence of death but had increased ascending aortic and branch diameters. Although NE infusion also increased systolic blood pressure, it did not affect mortality or enlarge aortic or branch diameters in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice. MicroCT identified novel pathological changes during AngII infusion, including development of aortic branch aneurysms in the celiac and superior mesenteric arteries; however, the maximal diameters of the adjacent suprarenal aorta showed only modest increases in male\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>\n                    AngII exacerbated aortic pathology in\n                    <jats:italic>Fbn1<\/jats:italic>\n                    <jats:sup>C1041G\/+<\/jats:sup>\n                    mice. It also promoted development of pathologies at aortic branch points, including the celiac and superior mesenteric arteries.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.11.26.690689","type":"posted-content","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T03:00:14Z","timestamp":1764558014000},"source":"Crossref","is-referenced-by-count":2,"title":["Angiotensin II Induces Abdominal Aortic Branch Aneurysms in\n                  <i>\n                    Fibrillin-1\n                    <sup>C1041G\/+<\/sup>\n                  <\/i>\n                  Mice"],"prefix":"10.64898","author":[{"given":"Michael K.","family":"Franklin","sequence":"first","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Howatt","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J.","family":"Moorleghen","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary B.","family":"Sheppard","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"},{"name":"Saha Aortic Center, University of Kentucky, Lexington, KY"},{"name":"Department of Physiology, University of Kentucky, Lexington, KY"},{"name":"Department of Family and Community Medicine, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0188-8094","authenticated-orcid":false,"given":"Yuriko","family":"Katsumata","sequence":"additional","affiliation":[{"name":"Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY"},{"name":"Division of Biomedical Informatics, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0017-6236","authenticated-orcid":false,"given":"Hisashi","family":"Sawada","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"},{"name":"Saha Aortic Center, University of Kentucky, Lexington, KY"},{"name":"Department of Physiology, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0577-2558","authenticated-orcid":false,"given":"Hong S.","family":"Lu","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"},{"name":"Saha Aortic Center, University of Kentucky, Lexington, KY"},{"name":"Department of Physiology, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2093-3775","authenticated-orcid":false,"given":"Alan","family":"Daugherty","sequence":"additional","affiliation":[{"name":"Saha Cardiovascular Research Center, University of Kentucky, Lexington, KY"},{"name":"Saha Aortic Center, University of Kentucky, Lexington, KY"},{"name":"Department of Physiology, University of Kentucky, Lexington, KY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026032716251147000_2025.11.26.690689v2.1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/s41572-021-00298-7","article-title":"Marfan syndrome","volume":"7","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"2026032716251147000_2025.11.26.690689v2.2","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1016\/j.avsg.2022.08.005","article-title":"Extrathoracic aneurysms in Marfan syndrome: A systematic review of the literature","volume":"87","year":"2022","journal-title":"Ann Vasc Surg"},{"key":"2026032716251147000_2025.11.26.690689v2.3","doi-asserted-by":"crossref","first-page":"3005","DOI":"10.1016\/j.jacc.2021.04.054","article-title":"Aortic branch aneurysms and vascular risk in patients with Marfan syndrome","volume":"77","year":"2021","journal-title":"J Am Coll Cardiol"},{"key":"2026032716251147000_2025.11.26.690689v2.4","doi-asserted-by":"crossref","unstructured":"Summers KM . 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