{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:34:22Z","timestamp":1790433262542,"version":"4.1.0"},"reference-count":47,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T00:00:00Z","timestamp":1560297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560151"],"award-info":[{"award-number":["81560151"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010857","name":"Jiangxi Provincial Department of Science and Technology","doi-asserted-by":"publisher","award":["20181BAB205022"],"award-info":[{"award-number":["20181BAB205022"]}],"id":[{"id":"10.13039\/501100010857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\/\u03b2-catenin pathway and that activation or inhibition of the Wnt\/\u03b2-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\/\u03b2-catenin pathway and promote intracellular cholesterol accumulation, both of which can contribute to the induction of ER stress and finally lead to ED.<\/jats:p>","DOI":"10.3390\/ijms20122861","type":"journal-article","created":{"date-parts":[[2019,6,12]],"date-time":"2019-06-12T10:55:19Z","timestamp":1560336919000},"page":"2861","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Sphingomyelin Synthase 2 Promotes Endothelial Dysfunction by Inducing Endoplasmic Reticulum Stress"],"prefix":"10.3390","volume":"20","author":[{"given":"Lingyue","family":"Hua","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruilin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuanhong","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiatian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"He","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lehan","family":"Yu","sequence":"additional","affiliation":[{"name":"School of Basic Medical Experiments Center, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nianlong","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, School of Basic Medical Science, Nanchang University, Nanchang 330006, Jiangxi, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,6,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1056\/NEJM199901143400207","article-title":"Atherosclerosis\u2014An Inflammatory Disease\u2014NEJM","volume":"340","author":"Ross","year":"1999","journal-title":"N. 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