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

摘要: Objective Hyperphosphatemia-induced endothelial dysfunction has been shown to play a pathogenic role in the development of atherosclerosis chronic kidney disease (CKD) through unclear mechanisms. Emerging evidence indicates that autophagy is involved maintenance normal cardiovascular function. However, it whether participates molecular mechanism underlying high phosphate (Pi)-induced dysfunction. Methods The activity was determined by immunofluorescence staining expression microtubule-associated protein 1 light chain 3 (LC3) 5/6 nephrectomy rat model CKD and sham-operated control rats. LC3-II/LC3-I ratio activation Akt/mammalian target rapamycin (mTOR) signaling pathway were cultured human microvascular cell (HMEC-1) cells exposed concentration Pi with or without influx blocker phosphonoformic acid, inhibitor 3-methyladenine, inducer rapamycin. impacts on Pi-induced apoptotic damage assessed flow cytometry. Results in vivo revealed hyperphosphatemia associated increased LC3 staining. exposure HMEC-1 cells induced both dose-dependent time-dependent increases accompanied inhibition Akt/mTOR pathway. In HMEC-1 cells, reversed acid blockage influx. Apoptosis, characterized levels cleaved caspase poly(ADP-ribose) polymerase, along Pi, 3-methyladenine significantly aggravated apoptosis. cytometry results confirmed promoted apoptosis cells. Conclusions Hyperphosphatemia induces autophagy, possibly pathway, which may protective against