AMPK α is active in autophagy of endothelial cells in arsenic-induced vascular endothelial dysfunction by regulating mTORC1\ p70S6K\ULK1

Chem Biol Interact. 2023 Dec 13:110832. doi: 10.1016/j.cbi.2023.110832. Online ahead of print.ABSTRACTCardiovascular disease (CVD) is the most common cause of death, environmental factors, such as arsenic, playing an important role in the progress of CVD. Vascular endothelial dysfunction (VED) is a crucial early feature for CVD, inorganic arsenic (iAs) can induce autophagy in various cells. However, the role of endothelial autophagy has rarely been studied in VED triggered by arsenic. Total of one hundred and twenty healthy male C57BL/6J mice weighing 18-22 g were randomly divided into an arsenic-exposure group and a control group for 3, 6, 9, and 12 weeks. The results showed that, independent of the exposure period, autophagy markers of p-ATG16L1 levels and Beclin 1 contents in the aortic arch endothelium increased significantly compared with those of the corresponding control group. And different exposure duration decreased NO contents in the serum significantly. Combined with the histological changes that endothelial injury aggravated gradually with the increasing exposure period, suggesting that under exposure to iAs over 9 weeks, VED was remarkably induced, and consistant high levels of endothelial autophagy may play an important role. Additionally, levels of p-AMPKα/AMPKα increased significantly and p-mTORC1/mTORC1 levels decreased remarkably in the aortic arch endothelium. Then, a NaAsO2-induced-VED in vitro model was used to explore the mechanism of arsenic-induced ...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Source Type: research