Collagen structure within aneurysm tissue in bicuspid aortic valve patients

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2025-01-31
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Abstract

Aortic aneurysms pose a substantial clinical problem, especially in individuals with bicuspid aortic valve (BAV) disease, as aneurysm formation is 50% more common in these populations. Although the exact cause of aortic aneurysms in BAV patients is still unknown, a growing body of research points to changes in the elastin and collagen composition of the aneurysm tissue as a key component influencing the course of the disease. The purpose of this thesis is to clarify collagen's contributions to aneurysm development, progression, and clinical consequences by examining its presence and type within aneurysm tissue in BAV patients and exploring the relationship between collagen content and type and its mechanical characteristics assessed on the same tissue patients. For this purpose we followed three steps including 1) developing a protocol to extract the protein from the tissue and performing ELISA tests; 2) examining the changes in the structure of the tissue before and after the tissue processing using SEM images for a representative sample, and 3) comparing the ELISA results to the mechanical properties obtained on the same tissue specimens -same region and same layer - to explore the possible correlation between the collagen content and the mechanical properties. The analysis of collagen composition and mechanical properties on the same tissues revealed some interesting results; first of all, high Wall Shear Stress (WSS) in the greater curvature region correlated with lower collagen content in Greater Curvature (GC). Further, we found that higher collagen contents correlated with stiffness but not strength. Moreover, results for both collagen-I ɑ-2 and collagen-III showed a bimodal distribution with a clear patient effect: for each patient with a high amount of collagen-III, the amount of collagen-I ɑ-2 was also high, regardless of layer and region, suggesting that collagen deposition could be different in different patients, possibly on account of the different stage/progression of the disease, as well as differences in genetics. These findings suggest a specific collagen signature associated with aortic pathophysiology in BAV patients. Further studies should clarify whether the patient-specific differences observed are associated with disease development and if lack of collagen renewal plays a role in aneurysm progression.

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Bozorgmehr, Z. (2025). Collagen structure within aneurysm tissue in bicuspid aortic valve patients (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.