Spatial Analysis of Microcalcification in Thoracic Aortic Aneurysms

Aortic medial microcalcification (AMC) is associated with cardiovascular risk, but its role in thoracic aortic aneurysm (TAA) remains unclear. This thesis examines the pathological and molecular characteristics of AMC in thoracic aortic samples from 117 TAA patients (bicuspid and sporadic) and 11 non-TAA control aortas, using quantitative histology and spatial transcriptomics. AMC was observed in 47% of the subject aortas, but no more prevalent in TAA compared to control aortas. AMC burden was higher in bicuspid TAAs than sporadic and showing a biphasic relationship with aortic diameter. Microcalcification occurred primarily in the mid-media and correlated with elastin content, but notably spared regions surrounding penetrating vasa vasorum. Spatial transcriptomics revealed that smooth muscle cells (SMC) surrounding vasa vasorum display preserved contractile pathways and osteoclast-like calcium-clearing features. This work highlights how local microvascular environments and endothelial-SMC interactions may influence AMC, offering insights for future therapies in aneurysm management.