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Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis

BACKGROUND: FGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Despite intensive study of the metabolic functions of FGF21, its important role in heart disease needs further exploration. Apoptosis induced by ox-LDL in vascular endothelial cells...

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Autores principales: Yan, Xinxin, Gou, Zhongshan, Li, Yuan, Wang, Yu, Zhu, Jingyan, Xu, Guidong, Zhang, Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114502/
https://www.ncbi.nlm.nih.gov/pubmed/30157856
http://dx.doi.org/10.1186/s12944-018-0846-x
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author Yan, Xinxin
Gou, Zhongshan
Li, Yuan
Wang, Yu
Zhu, Jingyan
Xu, Guidong
Zhang, Qian
author_facet Yan, Xinxin
Gou, Zhongshan
Li, Yuan
Wang, Yu
Zhu, Jingyan
Xu, Guidong
Zhang, Qian
author_sort Yan, Xinxin
collection PubMed
description BACKGROUND: FGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Despite intensive study of the metabolic functions of FGF21, its important role in heart disease needs further exploration. Apoptosis induced by ox-LDL in vascular endothelial cells is an important step in the progress of atherosclerosis. METHODS: The effects of FGF21 treatment on apoptosis induced by ox-LDL were tested in HUVECs. The role of FGF21 in atherosclerosis was studied by evaluating its function in apolipoprotein E double knockout (apoE−/−) mice. RESULTS: We found that apoptosis in HUVECs was alleviated by FGF21 treatment. The effects of FGF21 were independent of the ERK1/2 pathway and were mediated through inhibition of the Fas signaling pathway. FGF21 suppressed the development of atherosclerosis, and the administration of FGF21 ameliorated Fas-mediated apoptosis in apoE−/− mice. CONCLUSION: FGF21 protects against apoptosis in HUVECs by suppressing the expression of Fas; furthermore, FGF21 alleviated atherosclerosis by ameliorating Fas-mediated apoptosis in apoE−/− mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-018-0846-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-61145022018-09-04 Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis Yan, Xinxin Gou, Zhongshan Li, Yuan Wang, Yu Zhu, Jingyan Xu, Guidong Zhang, Qian Lipids Health Dis Research BACKGROUND: FGF21 is a critical endogenous regulator in energy homeostasis and systemic glucose and lipid metabolism. Despite intensive study of the metabolic functions of FGF21, its important role in heart disease needs further exploration. Apoptosis induced by ox-LDL in vascular endothelial cells is an important step in the progress of atherosclerosis. METHODS: The effects of FGF21 treatment on apoptosis induced by ox-LDL were tested in HUVECs. The role of FGF21 in atherosclerosis was studied by evaluating its function in apolipoprotein E double knockout (apoE−/−) mice. RESULTS: We found that apoptosis in HUVECs was alleviated by FGF21 treatment. The effects of FGF21 were independent of the ERK1/2 pathway and were mediated through inhibition of the Fas signaling pathway. FGF21 suppressed the development of atherosclerosis, and the administration of FGF21 ameliorated Fas-mediated apoptosis in apoE−/− mice. CONCLUSION: FGF21 protects against apoptosis in HUVECs by suppressing the expression of Fas; furthermore, FGF21 alleviated atherosclerosis by ameliorating Fas-mediated apoptosis in apoE−/− mice. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12944-018-0846-x) contains supplementary material, which is available to authorized users. BioMed Central 2018-08-29 /pmc/articles/PMC6114502/ /pubmed/30157856 http://dx.doi.org/10.1186/s12944-018-0846-x Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Yan, Xinxin
Gou, Zhongshan
Li, Yuan
Wang, Yu
Zhu, Jingyan
Xu, Guidong
Zhang, Qian
Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title_full Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title_fullStr Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title_full_unstemmed Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title_short Fibroblast growth factor 21 inhibits atherosclerosis in apoE−/− mice by ameliorating Fas-mediated apoptosis
title_sort fibroblast growth factor 21 inhibits atherosclerosis in apoe−/− mice by ameliorating fas-mediated apoptosis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6114502/
https://www.ncbi.nlm.nih.gov/pubmed/30157856
http://dx.doi.org/10.1186/s12944-018-0846-x
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