Abstract 17100: Cardiotonic Steroids Promote Renal Fibrosis and Dysfunction via NaK-ATPase Profibrotic Signaling in Heart Failure

Introduction: Patients with heart failure such as those following myocardial infarction often experience progressive cardio-renal compromise (or “cardio-renal syndrome”), leading to recurrent hospitalizations and clinical deterioration. As our mechanistic understanding of cardio-renal syndrome is lacking, there are limited treatment options beyond contemporary therapies of neurohormonal blockade. Cardiotonic steroids (CTS) are Na/K-ATPase (NKA-α-1) ligands that are elevated in clinical and experimental heat failure, but their role in renal disease progression in this setting is unclear. Hypothesis: We tested the hypothesis that CTS promote renal fibrosis and dysfunction in a process involving signaling through the NKA-α-1. Methods/Results: First, we performed left anterior descending coronary artery ligation (LADx) on mice expressing wild type NKA-α-1 (WT), as well as mice expressing transgenic human NKA-α-1 (NKA-Tg), which renders them more sensitive to CTS. NKA-Tg mice demonstrated increased renal fibro...