Abstract 14293: Sex Differences in Cytokine and Chemokine Expression in an Experimental AAA Rodent Model

Abstract

Introduction: Abdominal aortic aneurysms (AAAs) are a multifactorial disease process that results from a series of biomolecular processes. AAAs are more prevalent in men; however, women are at greater risk of rupture. Despite continued investigation, the mechanisms of sex disparities in AAA remain unknown. Hypothesis We hypothesize that male and female rats will have different inflammatory cytokine and chemokine expression in AAA tissue. Methods: Male and female Sprague-Dawley rats underwent intraluminal infrarenal abdominal aortic exposure to elastase to induce AAA. Rats were administered daily β-aminopropionitrile to promote AAA rupture. In vivo aortic diameters were evaluated using ultrasound (12MHz) at day 7 and 14 post-AAA induction. PET imaging with 64 Cu-DOTA-ECL1i (a selective radio-marker for C-C chemokine receptor type 2; CCR2), AAA tissue zymography and cytokine array were performed at day 6 and 14 to evaluate CCR2, matrix metalloproteinases (MMP), chemokine, and cytokine content. Results: Male rats developed larger AAAs at day 7 and 14 compared to female rats (p<0.0001; Figure 1A), but AAA rupture rate was similar between sexes. At day 6, AAA cytokine arrays demonstrated Rantes, IFN-y, and IL-17A were higher in males (p<0.01; Figure 1B-D). However, MCP-1, IL-6, IL-10, IL-18, IL-1B, and TNF-α were similar between groups (Figure 1E-J). Interestingly, at day 14, females showed significantly higher MCP-1, IL-6, and IL-10 (p<0.05; Figure 1E-G). PET imaging demonstrated that males had higher CCR2 uptake at day 14 (p<0.05; Figure 1K). AAA zymography demonstrated equivalent levels of total MMP-9, pro-MMP 9, and active MMP-9 between groups (Figure 1L-O). Conclusion Our findings demonstrated that inflammatory cytokines and chemokines are differentially expressed in AAA tissue - particularly CCR2 which is higher in males. This provides sex-specific AAA tissue targets for diagnostic molecular imaging and potential future immune-modulation strategies.