{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T11:08:33Z","timestamp":1774696113712,"version":"3.50.1"},"posted":{"date-parts":[[2023,5,12]]},"group-title":"Genetics","reference-count":36,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,5,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Marfan syndrome causes a hereditary form of thoracic aortic aneurysms with dilation of the aortic root. Human and animal models suggest a worse phenotype for males compared to females with respect to aneurysm size and risk of dissection. In this study we examine the effects of 17 \u03b2-estradiol on aortic dilation and rupture in a Marfan mouse model. Marfan male mice were administered 17 \u03b2-estradiol and the growth in aortic root size along with the risk of aortic rupture or dissection with the addition of angiotensin II was measured. Transcriptomic profiling was used to identify enriched pathways from 17 \u03b2-estradiol treatment. Aortic smooth muscle cells were then treated with cytokines in order to validate the mechanism of 17 \u03b2-estradiol protection. We show that 17 \u03b2-estradiol decreased the size and rate of aortic root dilation and improved survival from rupture and dissection after treatment with angiotensin II. The Marfan transcriptome was enriched in inflammatory genes and the addition of 17 \u03b2-estradiol modulated a set of genes that function through TNF\u03b1 mediated NF-\u03baB signaling. These included many proteins known to play a role in the phenotypic shift of aortic smooth muscle cells from a contractile to a more inflammatory-like state such as Vcam-1, Mcp-1, Lgals3, Il-6, Il-1b, and C3. In addition, 17 \u03b2-estradiol suppressed the induction of these TNF\u03b1 induced genes in aortic smooth muscle cells in vitro and this effect appears to be NF-\u03baB dependent. In conclusion, 17 \u03b2-estradiol protects against the dilation and rupture of aortic roots in Marfan male mice through the inhibition of TNF\u03b1 -NF-\u03baB signaling and thus prevents the phenotypic switch of aortic smooth muscle cells from a contractile to an inflammatory state.<\/jats:p>","DOI":"10.1101\/2023.05.09.540071","type":"posted-content","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T17:45:14Z","timestamp":1683913514000},"source":"Crossref","is-referenced-by-count":1,"title":["17 \u03b2-estradiol impedes aortic root dilation and rupture in male Marfan mice"],"prefix":"10.64898","author":[{"given":"Louis","family":"Saddic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean","family":"Escopete","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lior","family":"Zilberberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon","family":"Kalsow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Divya","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mansoureh","family":"Egbhali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Parker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023051504300479000_2023.05.09.540071v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.02.015"},{"key":"2023051504300479000_2023.05.09.540071v1.2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003792"},{"key":"2023051504300479000_2023.05.09.540071v1.3","doi-asserted-by":"publisher","DOI":"10.1053\/j.semtcvs.2011.08.009"},{"key":"2023051504300479000_2023.05.09.540071v1.4","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000143386.26399.84"},{"key":"2023051504300479000_2023.05.09.540071v1.5","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000085842.20866.6A"},{"key":"2023051504300479000_2023.05.09.540071v1.6","doi-asserted-by":"crossref","first-page":"H44","DOI":"10.1152\/ajpheart.00255.2021","article-title":"Age and sex dependency of thoracic aortopathy in a mouse model of Marfan syndrome","volume":"322","year":"2022","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2023051504300479000_2023.05.09.540071v1.7","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00933"},{"key":"2023051504300479000_2023.05.09.540071v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/s00392-016-1028-3"},{"key":"2023051504300479000_2023.05.09.540071v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.04.098"},{"key":"2023051504300479000_2023.05.09.540071v1.10","doi-asserted-by":"crossref","first-page":"e015773","DOI":"10.1161\/JAHA.119.015773","article-title":"Androgens Accentuate TGF-\u03b2 Dependent Erk\/Smad Activation During Thoracic Aortic Aneurysm Formation in Marfan Syndrome Male Mice","volume":"9","year":"2020","journal-title":"Journal of the American Heart Association"},{"key":"2023051504300479000_2023.05.09.540071v1.11","doi-asserted-by":"crossref","first-page":"H416","DOI":"10.1152\/ajpheart.00865.2005","article-title":"Flutamide restores cardiac function after trauma-hemorrhage via an estrogen-dependent pathway through upregulation of PGC-1","volume":"290","year":"2006","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2023051504300479000_2023.05.09.540071v1.12","doi-asserted-by":"publisher","DOI":"10.1210\/jc.76.5.1147"},{"key":"2023051504300479000_2023.05.09.540071v1.13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00217.2016"},{"key":"2023051504300479000_2023.05.09.540071v1.14","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.182279"},{"key":"2023051504300479000_2023.05.09.540071v1.15","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000214999.12921.4f"},{"key":"2023051504300479000_2023.05.09.540071v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2007.12.063"},{"key":"2023051504300479000_2023.05.09.540071v1.17","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.105.601674"},{"key":"2023051504300479000_2023.05.09.540071v1.18","unstructured":"S A. 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