Hyperphosphatemia induces protective autophagy in endothelial cells through the inhibition of Akt/mTOR signaling

Hyperphosphatemia associated with endothelial dysfunction contributes to increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD), but no definitive pathogenic mechanisms have been defined. This study demonstrated that CKD rats are characterized by hyperphosphatemia and increased autophagy activity in endothelial cells. In vitro, we found that hyperphosphatemia-induced endothelial autophagy through inhibition of the Akt/mammalian target of rapamycin signaling pathway, which may play a protective role against high Pi-induced apoptosis. Development of autophagy-targeting therapies may benefit the prevention of high Pi-related endothelial dysfunction in the pathogenesis of atherosclerosis in CKD.