# Heterogeneity of Ex Vivo and In Vivo Properties along the Length of the Abdominal Aortic Aneurysm
## 4 Discussion
Histological samples allowed for the analysis of aortic wall structure and composition as it relates to the mechanical properties of the aorta. More than 50% of these specimens presented non-discernible media, indicative of high degeneration and loss of structural integrity in the aortic tissue under investigation. Elastin, smooth muscle cells, and proteoglycans contents were assessed in the remaining samples. While elastin has been reported to be reduced in aneurysms [17], with ruptured AAAs presenting lower elastin content than non-ruptured ones [41], the regional heterogeneity of elastin content has not been previously reported. Present results showed no effect of the position along the length of the aorta on the content of medial constituents, but a significant effect of the circumferential position was found. Elastin and proteoglycans were observed to be present in inverse proportions with smooth muscle (i.e., an increase in relative elastin and proteoglycans is associated with a decrease in smooth muscle). Of note, specimens collected from the anterior regions of the aorta presented significantly lower elastin content compared to posterior regions. As previously discussed, the only other parameter significantly affected by the position along the circumference was the LTM that characterizes the elastin-dominated mechanical behavior of the tissue at low strain. Greater elastin content and higher LTM in posterior regions of the aorta indicate an asymmetric remodeling and degenerative process at the wall, with asymmetric growth and thrombus accumulation occurring predominantly in the anterior bulging. Literature findings suggest that the AAA pathophysiology is a multifactorial process, with cellular mechanisms integrally involved in the structural and functional changes that occur in the aortic wall. However, relatively few studies have investigated the heterogeneity of inflammatory response in human AAA and its possible implications. An effect of circumferential position was previously reported by [PERSON] et al., who found that lateral regions of AAA exhibited increased inflammatory activity in the adventitia compared to anterior and posterior regions [16]. In contrast, the present study showed no significant variation in inflammatory cell count among circumferential regions, although it should be noted that different inflammation markers were analyzed. However, when the effect of axial position was investigated, tissue samples showed significant heterogeneity in terms of inflammatory infiltrates. Higher inflammatory cell activity (CD4+, CD8+) in the adventitia was found in samples collected from regions in position 4 compared to position 2 and 3. The localized increase in helper T-cells (CD4+) and cytotoxic T-cells (CD8+) together in this region suggests the presence of CD4+ T-cell phenotype Th1, which has been implicated in ECM degradation [42]. CD4+ T-cells were also reported to release cytokines that stimulate angiogenesis and fibroblastic collagen accumulation in the adventitia. Therefore, their appearance is highly indicative of aortic wall remodeling [43; 44]. Interestingly, position 4 exhibited distinct mechanical behaviour compared to position 2 and 3, with a significantly higher TZO and TZe, possibly a result of increased fibrotic collagen deposition in the adventitia in combination with a degraded media. These results are significant in the overall discussion on AAA risk assessment: the axial heterogeneity in inflammatory cells seems to have direct functional implications that can be seen in the biomechanical results of this study. While the ex vivo mechanical and histological characterization of the aorta is essential for a thorough understanding of the structural and functional changes linked to AAA progression, the in vivo assessment becomes central when clinical application and disease management are the goal.