This series of infected EVARs is the largest group of infected AAA endografts reported to date. Because EVAR of AAAs is presently the most common method of repair, development of endograft infection, while rare, can be managed with acceptable mortality rates. Patients presenting with aortic-enteric fistula after EVAR appear to have a more virulent course.

Background-Our aim was to establish a novel model of abdominal aortic aneurysms (AAA) in mice using application of peri-adventitial elastase.

Diagnostic study, level III.

Background Deletion of Toll-like receptor 9 (Tlr9) signaling, which is important for sterile inflammatory processes, results in impaired venous thrombosis (VT) resolution in mice. The purpose of this study was to determine if deletion of Tlr9 affected sterile necrosis, apoptosis, and neutrophil extracellular trap (NET) production in VT. Methods Stasis and non-stasis murine models of VT were used in wild type (WT and Tlr9−/− mice, with assessment of VT size, and determination of neutrophil extracellular traps (NETs), necrosis and apoptosis markers. Anti-PMN and anti-platelet antibody strategies were used to determine the cellular roles and their roles in WT and Tlr9−/− mice. Results At 2d, stasis thrombi in Tlr9−/− mice were 62% larger (n = 6–10) with 1.4 fold increased uric acid levels, 1.7 fold more apoptotic cells, 2 fold increased citrullinated histones (cit-H3), 2 fold increased peptidylarginine deiminase – 4 and 1.5 fold increased elastase, with a 2.4 fold reduction in tissue factor pathway inhibitor (TFPI) as compared with WT (all n = 4–7; P < .05). In contrast, non-stasis VT sizes were not significantly different in Tlr9−/− mice (n = 4–6), and did not have elevated necrosis or NET markers. Stasis VT size was not reduced at the 2d time-point in WT or TLR9−/− mice that received treatment with DNAse-I, or in PAD4−/− mice, which are incapable of forming NETs. Stasis VT size was reduced 18% inTlr9−/− mice undergoing PMN depletion (n = 8–10), and was associated with 29 fold decreased cit H3, 1.3 fold decreased elastase, and 1.5 fold increased TFPI (all n = 6; P < .05). Lastly, platelet depletion (>90% reduction) did not significantly reduce stasis VT inTlr9−/− mice. Conclusions These data suggest the thrombogenic model impacts Tlr9 thrombogenic mechanisms, and that functional Tlr9 signaling in PMN, but not platelets or NETs, is an important mechanism in early stasis experimental venous thrombogenesis.

INTRODUCTION Estrogen receptor alpha (ERα) has been identified in the vessel wall, offering vasoprotective effects when upregulated. Estrogens are known to mediate the inflammatory mileu, and inflammation has long been associated with abdominal aortic aneurysm (AAA) formation. Therefore it is theorized that increased estrogen receptor in females contributes to their relative resistance to AAAs. The study’s objective was determining gender differences in ERα levels during experimental AAA formation. METHODS Infrarenal aortas of male and female C57 mice (n=18 and n=16, respectively) were infused with 0.4% elastase. Diameters were measured at day 0 and day 14. Aortic mRNA expression of ERα was determined on day 3 by RTPCR, while ERα protein levels were measured via Western blot. Immunohistochemistry using rabbit antibody for ERα was performed on day 14 samples and quantified. Zymography was done for MMP2 and 9 activity levels. Samples of human AAAs were collected and Western blot performed. Data were compared for significance using a student t-test. RESULTS Infrarenal aortic diameter increased in elastase-perfused males (ME) by 80% at 14 days post perfusion, while females (FE) increased by only 35% (p=0.0012). FE had 10x greater ERα mRNA expression compared with ME at day three (p=0.003). Similarly, ERα protein levels were 100% higher in FE compared to ME on day 14 (p=0.035). ERα protein levels were 80% higher in female human patients with AAA than in their male counterparts (p=0.029). ERα visualized via immunohistochemistry was 1.5 fold higher in FE than ME (p=0.029). MMP2 and 9 activity levels were decreased in female as compared with male aortas. CONCLUSION(S) This study demonstrates an increase in aortic wall ERα in females compared with males that correlates inversely with MMP activity and AAA formation. These findings, coupled with observations that exogenous estrogen inhibits AAA formation in males, further suggest that estrogen supplementation may be important to prevent AAA formation and growth.