Zachary Yoon-Kim
Research Mentor(s): Morgan Salmon
Mentor Department: Cardiac Surgery
Authors: Zachary Yoon-Kim, Matthew Kazaleh, Gorav Ailawadi, Morgan Salmon
Session: Session 5 (2:00pm – 2:50pm)
Presentation Type: Poster 70
Abstract
Previous studies have indicated that iron levels may affect the formation of Abdominal Aortic Aneurysms (AAAs). These levels are regulated by certain factors, including iron transport hormones, including hepcidin. Studies have shown that the removal of hepcidin may increase the incidence of the formation of AAAs. However, the effects of hepcidin levels based on sex have yet to be explored. This experiment’s goal was to determine if hepcidin has sex-dependent effects. Male and female wildtype-wildtype, wildtype-knockout, and knockout-knockout model mice were examined in one part of the study. Elastase was administered to the outer layer of the abdominal aorta, and on day 14, the mice were harvested. In an adjacent experiment, male and female hepcidin WT/WT and KO/KO mice underwent the elastase model with Beta-aminopropionitrile (BAPN) administration, with mice harvested on day 28. Mice were analyzed using immuno-histochemistry for cells important in AAAs. In male hepcidin models, WT/KO and KO/KO models exhibited smaller dilations compared to the WT/WT models (WT/WT 145.533.8% vs WT/KO 110.734.8% vs KO/KO 101.537.6%, p=0.0299). Additionally, the KO/KO models exhibited smaller dilations than the WT/KO. However, in female models, the effect was the opposite. The WT/KO and KO/KO models exhibited larger dilations compared to WT/WT models, with size increasing with less hepcidin (WT/WT 71.1522.0% vs WT/KO 101.625.9% vs KO/KO 119.023.5%, p =.0011). The same trends were seen in the BAPN/elastase model, in males (WT/WT 476.882.2%, KO/KO 196.031.9%, p=.0002) and females (WT/WT 186.726.0%, KO/KO 406.962.2%, p=0.0006). In conclusion, the removal of hepcidin in male mice exhibited a protective effect, where less hepcidin correlated to smaller dilation sizes. Conversely, in female mice, removal of hepcidin exhibited a negative effect, where less hepcidin correlated to larger dilation sizes. This indicates that hepcidin may be a sex-specific AAA treatment target, for which there may be significant clinical impacts.
