Age and Sex-Dependent Profiling of Angiotensin II Induced Thoracic Aortic Degeneration in Mice
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.