Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II–Induced Aortic Pathology
| Autor: | Lisa A. Cassis, Alan Daugherty, Yasir Alsiraj, Eric M. Blalock, Bradley S. Fleenor, Sean E. Thatcher |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Pathology X Chromosome Vascular Remodeling 030204 cardiovascular system & hematology Biology Y chromosome Article 03 medical and health sciences Aortic aneurysm Sex Factors Vascular Stiffness 0302 clinical medicine Aneurysm Y Chromosome Internal medicine medicine Animals Genetic Predisposition to Disease Testosterone Aorta Abdominal X chromosome Mice Knockout Sex Characteristics Autosome Angiotensin II medicine.disease Sex-Determining Region Y Protein Abdominal aortic aneurysm Mice Inbred C57BL Disease Models Animal Phenotype 030104 developmental biology Endocrinology Testis determining factor Receptors LDL cardiovascular system Female Cardiology and Cardiovascular Medicine Orchiectomy Aortic Aneurysm Abdominal Dilatation Pathologic |
| Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 38:143-153 |
| ISSN: | 1524-4636 1079-5642 |
| DOI: | 10.1161/atvbaha.117.310035 |
| Popis: | Objective— 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. Approach and Results— 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 saline or AngII and quantified mRNA abundance of key genes in both thoracic and abdominal aortas. Regional differences in mRNA abundance existed before AngII infusions, which were differentially influenced by AngII between genotypes. Prolonged AngII infusions resulted in aortic wall thickening of AAAs from XY males, whereas XX males had dilated focal AAAs. Conclusions— An XY sex chromosome complement mediates diffuse aortic pathology, whereas an XX sex chromosome complement contributes to focal AngII-induced AAAs. |
| Databáze: | OpenAIRE |
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