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Background: Marfan syndrome causes a hereditary form of TAA with dilation of the aortic root. Male patients with Marfan syndrome are more likely than women to have aortic dilation and dissection and mouse models of Marfan syndrome demonstrate larger aortic roots in males compared to females even after adjustment for body size. In this study we examine the effects of estrogen17 β-estradiol on aortic dilation and rupture in a Marfan mouse model. Methods: Marfan male mice were administered estrogen17 β-estradiol pellets with 60 day release and the growth in aortic root size was measured every 2 weeks for 8 weeks. Aortic root tissue from vehicle and 17 b-estradiol mice were subjected to proteomic analysis and bioinformatics was used to ascertain enriched pathways. Marfan mice with and without 17 b-estradiol were also treated with continuous angiotensin II infusion and survival was determined for 30 days. Results: Male Marfan mice with estrogen17 β-estradiol had a significant reduction in the ratio of aortic diameter 8 weeks after pellet implantation to baseline aortic diameter compared to the same ratio in Marfan mice with sham surgery. Proteomic analysis demonstrated complement C3 and C4 protein upregulation in Marfan mice compared to wild type and Marfan mice treated with 17 b-estradiol. Aortic smooth muscle cells express complement components in vivo and in vitro and expression of these factors are regulated by cytokines and estrogen17 β-estradiol in vitro. Additionally, 17 b-estradiol and female sex protect against aortic rupture when Marfan mice are treated with continuous infusion of angiotensin II and this protection correlates with lower protein levels of C3. Conclusions: Our findings support a protective role of 17 b-estradiol in preventing the dilation and rupture of aortic roots in Marfan male mice and suggest that these therapeutic actions may develop through anti-inflammatory properties. FAER Foundation for Anesthesia Education and Research This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.