Sphingomyelin synthase 2 promotes H2O2-induced endothelial dysfunction by activating the Wnt/β-catenin signaling pathway

Zhang,Panpan; Hua,Lingyue; Hou,Huan; Du,Xingyue; He,Zhiqiang; Liu,Menghan; Hu,Xiaojuan; Yan,Nianlong

doi:10.3892/ijmm.2018.3888

Sphingomyelin synthase 2 promotes H2O2-induced endothelial dysfunction by activating the Wnt/β-catenin signaling pathway

Authors:
- Panpan Zhang
- Lingyue Hua
- Huan Hou
- Xingyue Du
- Zhiqiang He
- Menghan Liu
- Xiaojuan Hu
- Nianlong Yan
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Affiliations: Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: September 19, 2018 https://doi.org/10.3892/ijmm.2018.3888
Pages: 3344-3354
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Atherosclerosis (AS) is the primary cause of various cardiovascular and cerebrovascular diseases and has high morbidity and mortality rates. Oxidative stress‑induced endothelial cells (ECs) dysfunction is the pathological basis of AS. In addition, sphingomyelin (SM) and the Wnt/β‑catenin signaling pathway are considered to be closely associated with AS; however, the specific mechanism is not clear. Therefore, the present study investigated whether SM may induce ECs dysfunction through the Wnt/β‑catenin signaling pathway. Firstly, a sphingomyelin synthase 2 (SMS2) overexpression cell model was constructed. It was identified that the expression of SMS2 was increased when ECs were treated with H2O2. In addition, these results demonstrated that SMS2 overexpression promoted apoptosis and macrophage adhesion of H2O2‑induced ECs, thereby increasing the expression of β‑catenin. Furthermore, SMS activity was inhibited with Dy105, combined with simultaneous treatment with LiCl or H2O2. This additionally confirmed that Dy105 significantly inhibited SMS activity and decreased the level of ECs dysfunction and β‑catenin content; however, LiCl served a key role in activating the Wnt/β‑catenin signaling pathway to promote ECs dysfunction. Collectively, these results suggested that SMS2 overexpression may promote ECs dysfunction by activating the Wnt/β‑catenin signaling pathway, while Dy105 may inhibit the evolution of oxidative stress‑induced dysfunction.

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