Mol. Cells 2018; 41(11): 900  https://doi.org/10.14348/molcells.2018.0111
Laminar Flow Inhibits ER Stress-Induced Endothelial Apoptosis through PI3K/Akt-Dependent Signaling Pathway
Suji Kim1, and Chang-Hoon Woo1,*
1Department of Pharmacology and Smart-Ageing Convergence Research Center, Yeungnam University College of Medicine,
Daegu 42415, Korea
Correspondence: changhoon_woo@yu.ac.kr
Received March 11, 2018; Revised October 15, 2018; Accepted October 23, 2018.; Published online November 1, 2018.
© Korean Society for Molecular and Cellular Biology. All rights reserved.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. To view a copy of this license, visit (http://creativecommons.org/licenses/by-nc-sa/3.0/).
ABSTRACT
Atherosclerosis preferentially involves in prone area of low and disturbed blood flow while steady and high levels of laminar blood flow are relatively protected from atherosclerosis. Disturbed flow induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). ER stress is caused under stress that disturbs the processing and folding of proteins resulting in the accumulation of misfolded proteins in the ER and activation of the UPR. Prolonged or severe UPR leads to activate apoptotic signaling. Recent studies have indicated that disturbed flow significantly up-regulated p-ATF6α, p-IRE1α, and its target spliced XBP-1. However, the role of laminar flow in ER stress-mediated endothelial apoptosis has not been reported yet. The present study thus investigated the role of laminar flow in ER stress-dependent endothelial cell death. The results demonstrated that laminar flow protects ER stress-induced cleavage forms of PARP-1 and caspase-3. Also, laminar flow inhibits ER stress-induced p-eIF2α, ATF4, CHOP, spliced XBP-1, ATF6 and JNK pathway; these effects are abrogated by pharmacological inhibition of PI3K with wortmannin. Finally, nitric oxide affects thapsigargin-induced cell death in response to laminar flow but not UPR. Taken together, these finding indicate that laminar flow inhibits UPR and ER stress-induced endothelial cell death via PI3K/Akt pathway.
Keywords: atherosclerosis, shear stress, endothelial cells, ER stress, unfolded protein response


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