Biochemical Profiling of Collagen and Elastin in Thoracic Aortic Aneurysms

Background: The complex pathophysiology of thoracic aortic aneurysm (TAA) remains only partially understood. Central to this condition are the structural imbalances of collagens and elastin, which are thought to be influenced by differing wall shear stress conditions and aortic valve pathologies impacting the blood flow. This study aims to describe their differences in expression in different areas of the aortic wall of TAA patients with different valve pathologies and morphologies.

Methods: Human TAA samples (n = 80) were separated into areas with higher (outer curvature, OC) and lower (inner curvature, IC) wall shear stress. A subgroup analysis was done including the four groups: Aortic insufficiency (AI) or stenosis (AS) and tricuspid (TAV) as well as bicuspid vales (BAV). Healthy samples (n = 10) from heart transplant donors (HTX) served as controls. RNA from both regions was extracted and expression analysis for collagens and elastin was performed via RT-qPCR. Results were expressed as multiples of IC (set to 1) expression. Furthermore, histological staining analysis of collagen and elastin was done on these samples. The tissue was provided by the cardiac surgery biobank at LMU Hospital.

Results: Significant increases in COL1A1 (1.46 ± 0.02, p = 0.03), 3A1 (1.22 ± 0.01, p = 0.03), 5A1 (1.54 ± 0.02, p = 0.02), and 11A1 (2.01 ± 0.03, p < 0.0001) were observed in the OC compared with the IC. Conversely, ELN levels were significantly lower (0.67 ± 0.01, p = 0.004) in the OC. Subgroup analysis revealed greater expressed COL1A1 and 5A1 in the OC of TAA with BAV (1.75 ± 0.04, p = 0.02 and 1.7 ± 0.05, p = 0.04) and AI (1.56 ± 0.03, p = 0.03 and 1.59 ± 0.05, p = 0.04). Meanwhile ELN expression was lower in the OC of TAA with TAV (0.65 ± 0.01, p = 0.02) and AS (0.64 ± 0.02, p = 0.03). Most significant differences, however, were measured in the expression of collagen 11A1, which was elevated in the OC of BAV, TAV, AI and AS respectively (2.31 ± 0.05, 1.84 ± 0.05, 2.16 ± 0.06 and 1.84 ± 0.04, p < 0.005). No significant differences were observed in the controls. Results were confirmed by histological examinations, which revealed an increase in collagen and a reduction in elastin staining in the OCs.

Conclusion: By analyzing collagen and elastin, key ECM proteins, this research provides unprecedented insights into structural integrity changes in different areas of the ascending aortic wall. We identified unique expression patterns of these proteins at the RNA level as well as on histology that may correlate with aneurysm development.

Publication History

Article published online:
11 February 2025