Digoxin

2ME and digoxin were purchased from Selleck Chemicals, Houston, and MP Biomedicals LLC, Solon, OH, respectively. Both compounds were freshly prepared in 0.5% carboxymethylcellulose/phosphate-buffered saline (PBS), and administered to mice at a dose of 50 mg/kg for 2ME, or 2 mg/kg for digoxin, per day via oral gavage. Dosages were selected based on those proven effective in prior published studies in other disease mouse models^{31 (link), 32 (link)}. To evaluate the effect of HIF-1α inhibitor treatment on AAA initiation and progression, treatment was initiated one day prior to, and terminated 14 days following, PPE infusion. To evaluate the effect on progression of existing AAAs, treatment was delayed until 4 days following PPE infusion and administered for a total of 10 days. Control mice for both groups were treated with equal volumes of vehicle over similar timeframes. In additional experiments, mice were treated with one of two mechanistically distinct PHD inhibitors, either cobalt chloride 30 mg/kg/d/ip (Alfa Aesar, Tewksbury, MA) or 1-(5-chloro-6-(trifluoromethoxy)-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid (JNJ-42041935), 100 μmoles/kg/d via oral gavage (Acme Bioscience, Inc., Palo Alto, CA), or vehicle alone, beginning one day prior to PPE infusion and continuing for 14 days^{33 (link), 34 (link)}