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

Area of Science:

• Cardiovascular Research
• Genetics and Genomics
• Endocrinology

Background:

• Aortic pathologies, including abdominal aortic aneurysms (AAAs), display sexual dimorphism, with higher prevalence in males.
• While less common in women, aortic aneurysms can progress more rapidly when they occur.
• Understanding the mechanisms behind these sex differences is crucial for targeted therapies.

Purpose of the Study:

• To investigate the distinct roles of sex chromosome complement (XY vs. XX) and testosterone in mediating angiotensin II (AngII)-induced aortic pathologies.
• To define the impact of sex chromosomes on the location and progression of aortic aneurysms.

Main Methods:

• Utilized transgenic low-density lipoprotein receptor-deficient (Ldlr-/-) male mice with XY or XX sex chromosome complements.
• Administered angiotensin II (AngII) infusion to induce aortic pathologies.
• Performed transcriptional profiling and quantified gene expression in thoracic and abdominal aortas; assessed effects of castration.

Main Results:

• XY males developed diffuse aortic aneurysm pathology, whereas XX males developed focal AAAs following AngII infusion.
• Castration significantly reduced AngII-induced aortic pathologies in both XY and XX males.
• XY males exhibited adventitial thickening in thoracic aortas, absent in XX males; XX males showed dilated focal AAAs.

Conclusions:

• An XY sex chromosome complement promotes diffuse aortic pathology.
• An XX sex chromosome complement contributes to the development of focal, dilated abdominal aortic aneurysms (AAAs).
• Sex chromosomes play a critical role in determining the pattern of aortic aneurysm formation.