Female Gender Attenuates Cytokine and Chemokine Expression and Leukocyte Recruitment in Experimental Rodent Abdominal Aortic Aneurysms

Abstract

Female gender appears to be protective in the development of abdominal aortic aneurysms (AAAs). This study sought to identify gender differences in cytokine and chemokine expression in an experimental rodent AAA model. Male and female rodent aortas were perfused with either saline (control) or elastase to induce AAA formation. Aortic diameter was determined and aortic tissue was harvested on postperfusion days 4 and 7. Cytokine and chemokine gene expression was examined using focused gene arrays. Immunohistochemistry was used to quantify aortic leukocyte infiltration. Data were analyzed by Student's t -tests and ANOVA. Elastase-perfused female rodents developed significantly smaller aneurysms compared to males by day 7 (93 10 vs. 201 25 , P 0.003). Elastase-perfused female aortas exhibited a fivefold decrease in expression of the BMP family and ligands of the TNF superfamily compared to males. In addition, the expression of members of the TGF and VEGF families were three to fourfold lower in female elastase-perfused aortas compared to males. Multiple members of the interleukin, CC chemokine receptor, and CC ligand families were detectable in only the male elastase-perfused aortas. Female elastase-perfused aortas demonstrated a corollary twofold lower neutrophil count (females: 17.5 1.1 PMN HPF; males: 41 5.2 neutrophils HPF, P 0.01) and a 1.5-fold lower macrophage count (females: 12 1.1 macrophages HPF; males: 17.5 1.1 macrophages HPF, P 0.003) compared to male elastase-perfused aortas. This study documents decreased expression of multiple cytokines and chemokines and diminished leukocyte trafficking in female rat aortas compared to male aortas following elastase perfusion. These genes may contribute to the gender disparity seen in AAA formation.