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Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo

Endoplasmic reticulum (ER) stress has been reported to be involved in many cardiovascular diseases such as atherosclerosis, diabetes, myocardial ischemia, and hypertension that ultimately result in heart failure. XBP1 is a key ER stress signal transducer and an important pro‐survival factor of the u...

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Autores principales: Duan, Quanlu, Ni, Li, Wang, Peihua, Chen, Chen, Yang, Lei, Ma, Ben, Gong, Wei, Cai, Zhejun, Zou, Ming‐Hui, Wang, Dao Wen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933664/
https://www.ncbi.nlm.nih.gov/pubmed/27133203
http://dx.doi.org/10.1111/acel.12460
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author Duan, Quanlu
Ni, Li
Wang, Peihua
Chen, Chen
Yang, Lei
Ma, Ben
Gong, Wei
Cai, Zhejun
Zou, Ming‐Hui
Wang, Dao Wen
author_facet Duan, Quanlu
Ni, Li
Wang, Peihua
Chen, Chen
Yang, Lei
Ma, Ben
Gong, Wei
Cai, Zhejun
Zou, Ming‐Hui
Wang, Dao Wen
author_sort Duan, Quanlu
collection PubMed
description Endoplasmic reticulum (ER) stress has been reported to be involved in many cardiovascular diseases such as atherosclerosis, diabetes, myocardial ischemia, and hypertension that ultimately result in heart failure. XBP1 is a key ER stress signal transducer and an important pro‐survival factor of the unfolded protein response (UPR) in mammalian cells. The aim of this study was to establish a role for XBP1 in the deregulation of pro‐angiogenic factor VEGF expression and potential regulatory mechanisms in hypertrophic and failing heart. Western blots showed that myocardial XBP1s protein was significantly increased in both isoproterenol (ISO)‐induced and pressure‐overload‐induced hypertrophic and failing heart compared to normal control. Furthermore, XBP1 silencing exacerbates ISO‐induced cardiac dysfunction along with a reduction of myocardial capillary density and cardiac expression of pro‐angiogenic factor VEGF‐A in vivo. Consistently, experiments in cultured cardiomyocytes H9c2 (2‐1) cells showed that UPR‐induced VEGF‐A upregulation was determined by XBP1 expression level. Importantly, VEGF‐A expression was increased in failing human heart tissue and blood samples and was correlated with the levels of XBP1. These results suggest that XBP1 regulates VEGF‐mediated cardiac angiogenesis, which contributes to the progression of adaptive hypertrophy, and might provide novel targets for prevention and treatment of heart failure.
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spelling pubmed-49336642016-08-01 Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo Duan, Quanlu Ni, Li Wang, Peihua Chen, Chen Yang, Lei Ma, Ben Gong, Wei Cai, Zhejun Zou, Ming‐Hui Wang, Dao Wen Aging Cell Original Articles Endoplasmic reticulum (ER) stress has been reported to be involved in many cardiovascular diseases such as atherosclerosis, diabetes, myocardial ischemia, and hypertension that ultimately result in heart failure. XBP1 is a key ER stress signal transducer and an important pro‐survival factor of the unfolded protein response (UPR) in mammalian cells. The aim of this study was to establish a role for XBP1 in the deregulation of pro‐angiogenic factor VEGF expression and potential regulatory mechanisms in hypertrophic and failing heart. Western blots showed that myocardial XBP1s protein was significantly increased in both isoproterenol (ISO)‐induced and pressure‐overload‐induced hypertrophic and failing heart compared to normal control. Furthermore, XBP1 silencing exacerbates ISO‐induced cardiac dysfunction along with a reduction of myocardial capillary density and cardiac expression of pro‐angiogenic factor VEGF‐A in vivo. Consistently, experiments in cultured cardiomyocytes H9c2 (2‐1) cells showed that UPR‐induced VEGF‐A upregulation was determined by XBP1 expression level. Importantly, VEGF‐A expression was increased in failing human heart tissue and blood samples and was correlated with the levels of XBP1. These results suggest that XBP1 regulates VEGF‐mediated cardiac angiogenesis, which contributes to the progression of adaptive hypertrophy, and might provide novel targets for prevention and treatment of heart failure. John Wiley and Sons Inc. 2016-05-01 2016-08 /pmc/articles/PMC4933664/ /pubmed/27133203 http://dx.doi.org/10.1111/acel.12460 Text en © 2016 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Duan, Quanlu
Ni, Li
Wang, Peihua
Chen, Chen
Yang, Lei
Ma, Ben
Gong, Wei
Cai, Zhejun
Zou, Ming‐Hui
Wang, Dao Wen
Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title_full Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title_fullStr Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title_full_unstemmed Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title_short Deregulation of XBP1 expression contributes to myocardial vascular endothelial growth factor‐A expression and angiogenesis during cardiac hypertrophy in vivo
title_sort deregulation of xbp1 expression contributes to myocardial vascular endothelial growth factor‐a expression and angiogenesis during cardiac hypertrophy in vivo
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4933664/
https://www.ncbi.nlm.nih.gov/pubmed/27133203
http://dx.doi.org/10.1111/acel.12460
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