eCite Digital Repository

Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression


Liu, J and Bi, X and Chen, T and Zhang, Q and Wang, SX and Chiu, JJ and Liu, GS and Zhang, Y and Bu, P and Jiang, F, Shear stress regulates endothelial cell autophagy via redox regulation and Sirt1 expression, Cell Death & Disease, 6 Article e1827. ISSN 2041-4889 (2015) [Refereed Article]


Copyright Statement

Copyright 2015 Macmillan Publishers Limited All rights reserved. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/cddis.2015.193


Disturbed cell autophagy is found in various cardiovascular disease conditions. Biomechanical stimuli induced by laminar blood flow have important protective actions against the development of various vascular diseases. However, the impacts and underlying mechanisms of shear stress on the autophagic process in vascular endothelial cells (ECs) are not entirely understood. Here we investigated the impacts of shear stress on autophagy in human vascular ECs. We found that shear stress induced by laminar flow, but not that by oscillatory or low-magnitude flow, promoted autophagy. Time-course analysis and flow cessation experiments confirmed that this effect was not a transient adaptive stress response but appeared to be a sustained physiological action. Flow had no effect on the mammalian target of rapamycin-ULK pathway, whereas it significantly upregulated Sirt1 expression. Inhibition of Sirt1 blunted shear stress-induced autophagy. Overexpression of wild-type Sirt1, but not the deacetylase-dead mutant, was sufficient to induce autophagy in ECs. Using both of gain- and loss-of-function experiments, we showed that Sirt1-dependent activation of FoxO1 was critical in mediating shear stress-induced autophagy. Shear stress also induced deacetylation of Atg5 and Atg7. Moreover, shear stress-induced Sirt1 expression and autophagy were redox dependent, whereas Sirt1 might act as a redox-sensitive transducer mediating reactive oxygen species-elicited autophagy. Functionally, we demonstrated that flow-conditioned cells are more resistant to oxidant-induced cell injury, and this cytoprotective effect was abolished after inhibition of autophagy. In summary, these results suggest that Sirt1-mediated autophagy in ECs may be a novel mechanism by which laminar flow produces its vascular-protective actions.

Item Details

Item Type:Refereed Article
Research Division:Biomedical and Clinical Sciences
Research Group:Medical biotechnology
Research Field:Gene and molecular therapy
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Liu, GS (Associate Professor Guei-Sheung Liu)
ID Code:120758
Year Published:2015
Web of Science® Times Cited:102
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-08-30
Last Modified:2017-11-03
Downloads:135 View Download Statistics

Repository Staff Only: item control page