Sex-Based Differences Among Experimental Swine Abdominal Aortic aneurysms

Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The

Sex hormones, specifically 17β-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.

Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n = 8), female (n = 5), and castrated male (n = 4) swine. Aortic dilation was measured on postoperative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17β-estradiol, and testosterone assay.

Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5% ± 11.4% versus 38.1% ± 4.5%, P = 0.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2% ± 7.5% versus 38.1% ± 4.5%, P = 0.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17β-estradiol compared with uncastrated males (1590 ± 873.3 ng/mL versus 95.2 ± 2.3 ng/mL, P = 0.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (P = 0.01 and <0 .01, respectively). No differences existed for T-cells or smooth muscle cells between groups. Multiple proinflammatory cytokines were elevated within uncastrated male aortic walls compared to females and castrated males. Conclusions: Sex hormones, specifically 17β-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.