Monosomy X in Female Mice Influences the Regional Formation and Augments the Severity of Angiotensin II-Induced Aortopathies.

Autor:	AlSiraj Y; Department of Pharmacology and Nutritional Sciences (Y.A., S.E.T., E.B., L.A.C.), University of Kentucky, Lexington., Thatcher SE; Department of Pharmacology and Nutritional Sciences (Y.A., S.E.T., E.B., L.A.C.), University of Kentucky, Lexington., Blalock E; Department of Pharmacology and Nutritional Sciences (Y.A., S.E.T., E.B., L.A.C.), University of Kentucky, Lexington., Saintilnord WN; Department of Molecular and Cellular Biochemistry (W.N.S.), University of Kentucky, Lexington., Daugherty A; Department of Physiology (A.D., H.S.L.), University of Kentucky, Lexington.; Saha Cardiovascular Research Center (A.D., H.S.L.), University of Kentucky, Lexington., Lu HS; Department of Physiology (A.D., H.S.L.), University of Kentucky, Lexington.; Saha Cardiovascular Research Center (A.D., H.S.L.), University of Kentucky, Lexington., Luo W; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston (W.L., Y.H.S., S.A.L.)., Shen YH; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston (W.L., Y.H.S., S.A.L.)., LeMaire SA; Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, and Department of Cardiovascular Surgery, Texas Heart Institute, Houston (W.L., Y.H.S., S.A.L.)., Arnold AP; Integrative Biology and Physiology, University of California, Los Angeles (A.P.A.)., Cassis LA; Department of Pharmacology and Nutritional Sciences (Y.A., S.E.T., E.B., L.A.C.), University of Kentucky, Lexington.
Jazyk:	angličtina
Zdroj:	Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 2021 Jan; Vol. 41 (1), pp. 269-283. Date of Electronic Publication: 2020 Oct 15.
DOI:	10.1161/ATVBAHA.120.314407
Abstrakt:	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:	MEDLINE
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