Shear stress induces human aortic endothelial cell apoptosis via interleukin‑1 receptor‑associated kinase 2‑induced endoplasmic reticulum stress

Pan,Longfei; Hong,Zhou; Yu,Lei; Gao,Yanxia; Zhang,Rui; Feng,Hui; Su,Lijuan; Wang,Gang

doi:10.3892/mmr.2017.7524

Shear stress induces human aortic endothelial cell apoptosis via interleukin‑1 receptor‑associated kinase 2‑induced endoplasmic reticulum stress

Authors:
- Longfei Pan
- Zhou Hong
- Lei Yu
- Yanxia Gao
- Rui Zhang
- Hui Feng
- Lijuan Su
- Gang Wang
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Affiliations: Department of Emergency Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Emergency Medicine, The Fifth Hospital of Xi'an, Xi'an, Shaanxi 710082, P.R. China, Department of Basic Medicine, Xi'an Medical College, Xi'an, Shaanxi 710068, P.R. China
Published online on: September 19, 2017 https://doi.org/10.3892/mmr.2017.7524
Pages: 7205-7212
Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis is characterized by localized lesions distributed in the arterial tree due to the shear stress produced by blood flow. Endothelial cells are directly affected by alterations in blood flow. Dysfunction and injury to endothelial cells has been hypothesized to initiate the pathological processes of atherosclerosis. The present study aimed to investigate the mechanism of shear stress‑induced endothelial cellular apoptosis. Shear stress was generated using an artificial device to mimic the impact of disturbed blood flow on cultured human aortic endothelial cells (HAECs). Cellular apoptosis was assessed using a terminal deoxynucleotidyl transferase dUTP nick end labeling assay; an ELISA assay was used to detect the produced interleukin (IL)‑1β; specific small interfering (si)RNA was used to knockdown the expression of interleukin‑1 receptor‑associated kinase 2 (IRAK2) in HAECs and the expression levels of 78 kDa glucose‑regulated protein, DNA damage‑inducible transcript 3 protein (CHOP), IRAK2 and IL‑1β were evaluated using western blotting. The results of the present study demonstrated that artificial shear stress induced endoplasmic reticulum (ER) stress, IL‑1β production and apoptosis in HAECs in a time‑dependent manner. The inhibition of ER stress, and treatment with interleukin‑1 receptor antagonist protein and siRNA against IRAK2 attenuated shear stress‑induced CHOP signaling‑mediated cellular apoptosis. Therefore, overproduction of IL‑1β exacerbated shear stress‑induced ER stress‑mediated apoptosis via the IRAK2/CHOP signaling pathway in endothelial cells.

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