Sex-Based Differences Among Experimental Swine Abdominal Aortic aneurysms.

The specific biological factors that confer protection against aortic wall weakening in females remain poorly understood. While clinical observations suggest sex-based disparities in aneurysm prevalence, the underlying physiological drivers are unclear. No prior work had resolved how hormonal environments dictate the structural integrity of the aorta in large animal models. That uncertainty drove the need for controlled experimental investigations into vascular pathology. Prior research has shown that male sex is often associated with higher risks of aortic disease. However, the exact contribution of circulating hormones to these outcomes has not been fully elucidated. This gap motivated a closer look at how different hormonal profiles impact vessel expansion. The current study addresses these questions by examining specific hormonal influences on aortic health.

The aim of this study was to explore the role of sex and sex hormones in the formation of abdominal aortic aneurysms. Researchers sought to clarify why female sex appears to offer protection against aortic wall weakening. This investigation focused on identifying the hormonal mechanisms that drive structural changes in the aorta. The study addressed the uncertainty surrounding how different hormonal environments influence vascular disease progression. By using a controlled animal model, the team intended to isolate the effects of testosterone and 17β-estradiol. No prior work had fully resolved the specific contributions of these hormones to aneurysm development in large mammals. This gap motivated a systematic comparison between uncastrated males, females, and castrated males. The project ultimately aimed to provide insights into the physiological drivers of aortic pathology.

The research team utilized a previously validated surgical approach to induce infrarenal aneurysms in three distinct groups of swine. These groups included uncastrated males, females, and castrated males to isolate hormonal variables. Postoperative monitoring occurred over a four-week period to track vascular changes. At the terminal procedure, investigators measured aortic diameters to determine the extent of dilation. Tissue samples underwent immunohistochemistry to evaluate cellular composition within the vessel walls. Cytokine arrays were performed to detect inflammatory markers present in the aortic tissue. Gelatin zymography assessed the enzymatic activity related to structural protein degradation. Finally, serum samples were analyzed to quantify the concentrations of circulating 17β-estradiol and testosterone.

Uncastrated males displayed the largest maximal aortic dilation at 113.5% compared to only 38.1% in castrated males. Females also showed significantly higher mean dilation than castrated males, reaching 96.2% during the observation period. No significant difference in aortic diameter existed between females and uncastrated males at the end of the study. Female swine maintained significantly higher 17β-estradiol levels than uncastrated males, measuring 1590 ng/mL versus 95.2 ng/mL. Elastin degradation was significantly more severe in uncastrated males than in the other two groups. Proinflammatory cytokines were consistently elevated within the aortic walls of uncastrated males. No significant variations in T-cell or smooth muscle cell counts were detected across the different cohorts. These results demonstrate that hormonal environments directly influence the severity of aneurysm formation and tissue remodeling.

The researchers propose that sex hormones significantly modulate the progression of aortic dilation in this porcine model. Uncastrated males exhibited more pronounced vessel expansion than both females and castrated males. These findings suggest that testosterone may contribute to the severity of aortic wall degradation. The data indicate that female hormonal profiles do not necessarily prevent expansion compared to castrated males. Elastin breakdown appears to be a primary mechanism distinguishing the male response from other groups. Proinflammatory cytokine levels were notably higher in the aortic walls of uncastrated males. These observations align with known patterns of vascular disease seen in human patients. The study highlights the complex interplay between endocrine status and structural aortic integrity.