Fewer females develop AADs (ascending aortic aneurysms and dissections) and the reasons for this protection remain poorly understood. The present study seeks to develop a mouse model that may be utilized to address this sexual dimorphism. Adult normolipidemic mice were challenged with BAPN (β‐aminopropionitrile), AngII (angiotensin II), or BAPN + AngII. An initial protocol optimization found that 0.2% BAPN in drinking water plus AngII‐infusion at 1,000 ng kg−1 min−1 produced favorable rates of AAD rupture (~50%) and dilation (~40%) in 28 days. Using these dosages, further experiments revealed that BAPN is toxic to naïve mature aortas and it acted synergistically with AngII to promote aortic tears and dissections. BAPN + AngII provoked early infiltration of myeloid cells and subsequent recruitment of lymphoid cells to the aortic wall. AADs established with BAPN + AngII, but not AngII alone, continued to expand after the cessation of AngII‐infusion. This indefinite growth precipitated a 61% increase in the AAD diameter in 56 days. More importantly, with the optimized protocol, significant differences in AAD dilation (p = .012) and medial degeneration (p = .036) were detected between male and female mice. Treatment of ovariectomized mice with estradiol protected AAD formation (p = .014). In summary, this study developed a powerful mouse AAD model that can be used to study the sexual dimorphism in AAD formation.

中文翻译：

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一种经过验证的小鼠模型，能够重现女性性激素对升主动脉瘤和夹层 (AAD) 的保护作用


患有 AAD（升主动脉瘤和夹层）的女性较少，而且这种保护的原因仍然知之甚少。本研究旨在开发一种可用于解决这种性别二态性的小鼠模型。成年正常血脂小鼠接受 BAPN（β-氨基丙腈）、AngII（血管紧张素 II）或 BAPN + AngII 攻击。初步方案优化发现，饮用水中的 0.2% BAPN 加上 1,000 ng kg−1 min−1 的 AngII 输注可在 28 天内产生良好的 AAD 破裂率 (~50%) 和扩张率 (~40%)。使用这些剂量，进一步的实验表明 BAPN 对幼稚成熟的主动脉具有毒性，并且它与 AngII 协同作用以促进主动脉撕裂和夹层。 BAPN + AngII 引发骨髓细胞的早期浸润，随后将淋巴细胞募集至主动脉壁。用 BAPN + AngII 而不是单独使用 AngII 建立的 AAD 在停止 AngII 输注后继续扩大。这种无限增长导致 AAD 直径在 56 天内增加了 61%。更重要的是，通过优化方案，在雄性和雌性小鼠之间检测到 AAD 扩张 (p = .012) 和内侧变性 (p = .036) 的显着差异。用雌二醇治疗切除卵巢的小鼠可以保护 AAD 的形成 (p = .014)。总之，本研究开发了一种强大的小鼠 AAD 模型，可用于研究 AAD 形成中的性别二态性。