Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II–Induced Aortopathies
| Autor: | Wesley N. Saintilnord, Ying H. Shen, Arthur P. Arnold, Alan Daugherty, Yasir Alsiraj, Scott A. LeMaire, Eric M. Blalock, Lisa A. Cassis, Wei Luo, Sean E. Thatcher, Hong Lu |
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| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
Ovariectomy Turner Syndrome Aorta Thoracic Disease Severity of Illness Index Article Internal medicine Turner syndrome Renin–angiotensin system Animals Medicine Aorta Abdominal Histone Demethylases Mice Knockout Monosomy X Aortic Aneurysm Thoracic business.industry Angiotensin II DNA Methylation medicine.disease Mice Inbred C57BL Disease Models Animal Endocrinology Receptors LDL cardiovascular system Female Cardiology and Cardiovascular Medicine business Aortic Aneurysm Abdominal |
| Zdroj: | Arterioscler Thromb Vasc Biol |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.120.314407 |
| Popis: | Objective: Turner syndrome women (monosomy X) have high risk of aortopathies consistent with a role for sex chromosomes in disease development. We demonstrated that sex chromosomes influence regional development of Ang II (angiotensin II)–induced aortopathies in mice. In this study, we determined if the number of X chromosomes regulates regional development of Ang II–induced aortopathies. Approach and Results: We used females with varying numbers of X chromosomes (XX female mice [XXF] or XO female mice [XOF]) on an C57BL/6J (ascending aortopathies) or low-density lipoprotein receptor deficient ( Ldlr −/− ) background (descending and abdominal aortopathies) compared with XY males (XYM). To induce aortopathies, mice were infused with Ang II. XOF (C57BL/6J) exhibited larger percent increases in ascending aortic lumen diameters than Ang II–infused XXF or XYM. Ang II–infused XOF ( Ldlr −/− ) exhibited similar incidences of thoracic (XOF, 50%; XYM, 71%) and abdominal aortopathies (XOF, 83%; XYM, 71%) as XYM, which were greater than XXF (XXF, 0%). Abdominal aortic lumen diameters and maximal external diameters were similar between XOF and XYM but greater than XXF, and these effects persisted with extended Ang II infusions. Larger aortic lumen diameters, abdominal aortopathy incidence (XXF, 20%; XOF, 75%), and maximal aneurysm diameters (XXF, 1.02±0.17; XOF, 1.96±0.32 mm; P =0.027) persisted in ovariectomized Ang II–infused XOF mice. Data from RNA-seq demonstrated that X chromosome genes that escape X-inactivation (histone lysine demethylases Kdm5c and Kdm6a ) exhibited lower mRNA abundance in aortas of XOF than XXF ( P =0.033 and 0.024, respectively). Conversely, DNA methylation was higher in aortas of XOF than XXF ( P =0.038). Conclusions: The absence of a second X chromosome promotes diffuse Ang II–induced aortopathies in females. |
| Databáze: | OpenAIRE |
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