Thesis Format
Monograph
Degree
Master of Science
Program
Biochemistry
Supervisor
Dr. J. Geoffrey Pickering
Abstract
The role of sex and age in thoracic aortic aneurysm (TAA) pathogenesis remains incompletely understood. Using an Angiotensin II-infused C57BL/6 mouse model, we investigated sex- and age-specific differences in vascular remodeling over 28 days. Transcriptomic profiling of vascular smooth muscle cells (VSMCs) microdissected from FFPE aortic media was performed using nCounter to identify molecular pathways underlying these differences. Younger female mice (6-9 months) exhibited resistance to ascending aortic dilation, associated with enhanced branched-chain amino acid (BCAA) catabolism and fatty acid metabolism, which may preserve VSMC function and vascular homeostasis. Conversely, younger males, older females, and males (13-15 months) demonstrated increased susceptibility, marked by dysregulated metabolic pathways and senescence-related signatures. These findings suggest that age- and sex-specific metabolic adaptations, revealed through transcriptomics, play a key role in vascular resilience or dysfunction. This study highlights potential therapeutic targets for at-risk populations.
Summary for Lay Audience
Thoracic aortic aneurysms (TAAs) are serious conditions where the wall of the aorta, the body’s largest artery, weakens and stretches, potentially leading to life-threatening complications such as a rupture. While men are generally more likely to develop TAAs, the role of biological sex in how the disease progresses is not fully understood. Our study focuses on exploring these differences in mice by comparing males and females at different ages to identify factors that might protect or predispose individuals to this condition.
We studied cells from the aortic wall, specifically vascular smooth muscle cells (VSMCs), which are critical for maintaining the strength and structure of the aorta. By analyzing the genetic activity within these cells using advanced techniques, we discovered that younger females are significantly less likely to experience TAA-related aortic dilation compared to other groups. This suggests that younger females may have protective biological mechanisms that reduce their risk of developing this dangerous condition.
Our findings point to differences in how certain metabolic pathways are upregulated in younger females. These pathways, responsible for breaking down branched-chain amino acids and fatty acids, may provide energy and resilience to the cells in their aortic walls, helping to maintain the aortas strength. In contrast, males and older mice seem to rely on different cellular processes, which may make their aortas more vulnerable to weakening and damage over time.
This research provides valuable insights into why younger females are less likely to develop TAA dilation, emphasizing the importance of understanding sex- and age-specific differences in diseases. By identifying these protective mechanisms, we hope to inspire new approaches to prevention and treatment, specific to the individuals age and sex. This work underscores the importance of personalized medicine in tackling complex health challenges and improving outcomes for those at risk of TAAs.
Recommended Citation
Marhon, Ali, "Age and Sex-Dependent Profiling of Angiotensin II Induced Thoracic Aortic Degeneration in Mice" (2025). Electronic Thesis and Dissertation Repository. 10678.
https://ir.lib.uwo.ca/etd/10678