Inflammation and DKK1-induced AKT activation contribute to endothelial dysfunction following NR2F2 loss
Edward J. Dougherty, Li‐Yuan Chen, Keytam S. Awad, Gabriela A. Ferreyra, Cumhur Y. Demirkale, Ali Keshavarz, Salina Gairhe, Kathryn A. Johnston, Madelyn E. Hicks, Alexis B. Sandler, Colleen S. Curran, Janell Krack, Yi Ding, Anthony F. Suffredini, Michael A. Solomon, Jason M. Elinoff, Robert L. Danner
Abstract
NR2F2 loss in the endothelial lining of blood vessels is associated with cardiovascular disease. Here, NR2F2-silenced human endothelial cells were inflammatory, proliferative, hypermigratory, and apoptosis-resistant with increased oxidant stress and endothelial-to-mesenchymal transition. DKK1 was induced in NR2F2-silenced endothelial cells, while co-silencing NR2F2 and DKK1 prevented NR2F2-loss-associated abnormalities in endothelial signaling and phenotype. Activating NR2F2 or blocking DKK1 may be useful therapeutic targets for treating vascular diseases associated with endothelial dysfunction.