A validated mouse model capable of recapitulating the protective effects of female sex hormones on ascending aortic aneurysms and dissections (AADs)

Autor: Xiaoyan Qi, Fen Wang, Changzoon Chun, Lennon Saldarriaga, Zhisheng Jiang, Eric Y. Pruitt, George J. Arnaoutakis, Gilbert R. Upchurch Jr, Zhihua Jiang
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Physiological Reports, Vol 8, Iss 22, Pp n/a-n/a (2020)
Druh dokumentu: article
ISSN: 2051-817X
DOI: 10.14814/phy2.14631
Popis: Abstract 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.
Databáze: Directory of Open Access Journals
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