Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II-Induced Aortic Pathology

Arteriosclerosis, Thrombosis, and Vascular Biology
Yasir AlsirajLisa A Cassis

Abstract

Aortic pathologies exhibit sexual dimorphism, with aneurysms in both the thoracic and abdominal aorta (ie, abdominal aortic aneurysm [AAA]) exhibiting higher male prevalence. Women have lower prevalence of aneurysms, but when they occur, aneurysms progress rapidly. To define mechanisms for these sex differences, we determined the role of sex chromosome complement and testosterone on the location and progression of angiotensin II (AngII)-induced aortic pathologies. We used transgenic male mice expressing Sry (sex-determining region Y) on an autosome to create Ldlr (low-density lipoprotein receptor)-deficient male mice with an XY or XX sex chromosome complement. Transcriptional profiling was performed on abdominal aortas from XY or XX males, demonstrating 1746 genes influenced by sex chromosomes or sex hormones. Males (XY or XX) were either sham-operated or orchiectomized before AngII infusions. Diffuse aortic aneurysm pathology developed in XY AngII-infused males, whereas XX males developed focal AAAs. Castration reduced all AngII-induced aortic pathologies in XY and XX males. Thoracic aortas from AngII-infused XY males exhibited adventitial thickening that was not present in XX males. We infused male XY and XX mice with either ...Continue Reading

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Dec 29, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Siddharth K Prakash, Dianna M Milewicz
Jun 29, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Chia-Hua WuHong S Lu
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Oct 16, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Yasir AlSirajLisa A Cassis
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