2. Academic Validation
  3. Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress

Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress

  • Int J Mol Sci. 2019 Jun 12;20(12):2861. doi: 10.3390/ijms20122861.
Lingyue Hua 1,  Na Wu 2,  Ruilin Zhao 3,  Xuanhong He 4,  Qian Liu 5,  Xiatian Li 6,  Zhiqiang He 7,  Lehan Yu 8,  Nianlong Yan 9
Affiliations

Affiliations

  • 1 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. hly3288551238@163.com.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. wn13907096825@163.com.
  • 3 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. zrl953226930@163.com.
  • 4 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. hxhxhong@163.com.
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. liucandice0412@163.com.
  • 6 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. 15807939939@163.com.
  • 7 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. hzq3231103954@163.com.
  • 8 School of Basic Medical Experiments Center, Nanchang University, Nanchang 330006, Jiangxi, China. yulehan@sohu.com.
  • 9 Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China. yannianlong@163.com.
PMID: 31212751 DOI: 10.3390/ijms20122861
Abstract

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.

Keywords

atherosclerosis; endoplasmic reticulum stress; endothelial dysfunction; sphingomyelin synthase 2; β-catenin.

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