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Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress
Endothelial dysfunction (ED) is an important contributor to atherosclerotic cardiovascular disease. Our previous study demonstrated that sphingomyelin synthase 2 (SMS2) promotes ED. Moreover, endoplasmic reticulum (ER) stress can lead to ED. However, whether there is a correlation between SMS2 and E...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627305/ https://www.ncbi.nlm.nih.gov/pubmed/31212751 http://dx.doi.org/10.3390/ijms20122861 |
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author | Hua, Lingyue Wu, Na Zhao, Ruilin He, Xuanhong Liu, Qian Li, Xiatian He, Zhiqiang Yu, Lehan Yan, Nianlong |
author_facet | Hua, Lingyue Wu, Na Zhao, Ruilin He, Xuanhong Liu, Qian Li, Xiatian He, Zhiqiang Yu, Lehan Yan, Nianlong |
author_sort | Hua, Lingyue |
collection | PubMed |
description | Endothelial dysfunction (ED) is an important contributor to atherosclerotic cardiovascular disease. Our previous study demonstrated that sphingomyelin synthase 2 (SMS2) promotes ED. Moreover, endoplasmic reticulum (ER) stress can lead to ED. However, whether there is a correlation between SMS2 and ER stress is unclear. To examine their correlation and determine the detailed mechanism of this process, we constructed a human umbilical vein endothelial cell (HUVEC) model with SMS2 overexpression. These cells were treated with 4-PBA or simvastatin and with LiCl and salinomycin alone. The results showed that SMS2 can promote the phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and activate the Wnt/β-catenin pathway and that activation or inhibition of the Wnt/β-catenin pathway can induce or block ER stress, respectively. However, inhibition of ER stress by 4-PBA can decrease ER stress and ED. Furthermore, when the biosynthesis of cholesterol is inhibited by simvastatin, the reduction in intracellular cholesterol coincides with a decrease in ER stress and ED. Collectively, our results demonstrate that SMS2 can activate the Wnt/β-catenin pathway and promote intracellular cholesterol accumulation, both of which can contribute to the induction of ER stress and finally lead to ED. |
format | Online Article Text |
id | pubmed-6627305 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66273052019-07-23 Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress Hua, Lingyue Wu, Na Zhao, Ruilin He, Xuanhong Liu, Qian Li, Xiatian He, Zhiqiang Yu, Lehan Yan, Nianlong Int J Mol Sci Article Endothelial dysfunction (ED) is an important contributor to atherosclerotic cardiovascular disease. Our previous study demonstrated that sphingomyelin synthase 2 (SMS2) promotes ED. Moreover, endoplasmic reticulum (ER) stress can lead to ED. However, whether there is a correlation between SMS2 and ER stress is unclear. To examine their correlation and determine the detailed mechanism of this process, we constructed a human umbilical vein endothelial cell (HUVEC) model with SMS2 overexpression. These cells were treated with 4-PBA or simvastatin and with LiCl and salinomycin alone. The results showed that SMS2 can promote the phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and activate the Wnt/β-catenin pathway and that activation or inhibition of the Wnt/β-catenin pathway can induce or block ER stress, respectively. However, inhibition of ER stress by 4-PBA can decrease ER stress and ED. Furthermore, when the biosynthesis of cholesterol is inhibited by simvastatin, the reduction in intracellular cholesterol coincides with a decrease in ER stress and ED. Collectively, our results demonstrate that SMS2 can activate the Wnt/β-catenin pathway and promote intracellular cholesterol accumulation, both of which can contribute to the induction of ER stress and finally lead to ED. MDPI 2019-06-12 /pmc/articles/PMC6627305/ /pubmed/31212751 http://dx.doi.org/10.3390/ijms20122861 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hua, Lingyue Wu, Na Zhao, Ruilin He, Xuanhong Liu, Qian Li, Xiatian He, Zhiqiang Yu, Lehan Yan, Nianlong Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title | Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title_full | Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title_fullStr | Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title_full_unstemmed | Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title_short | Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress |
title_sort | sphingomyelin synthase 2 promotes endothelial dysfunction by inducing endoplasmic reticulum stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627305/ https://www.ncbi.nlm.nih.gov/pubmed/31212751 http://dx.doi.org/10.3390/ijms20122861 |
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