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LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6
Coronary artery disease (CAD) is a major atherosclerotic cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of lncRNA non-coding RNA activated by DNA damage (NORAD) on atherosclerosis in CAD re...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301222/ https://www.ncbi.nlm.nih.gov/pubmed/34307380 http://dx.doi.org/10.3389/fcell.2021.701628 |
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author | Kai, Huihua Wu, Qiyong Yin, Ruohan Tang, Xiaoqiang Shi, Haifeng Wang, Tao Zhang, Ming Pan, Changjie |
author_facet | Kai, Huihua Wu, Qiyong Yin, Ruohan Tang, Xiaoqiang Shi, Haifeng Wang, Tao Zhang, Ming Pan, Changjie |
author_sort | Kai, Huihua |
collection | PubMed |
description | Coronary artery disease (CAD) is a major atherosclerotic cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of lncRNA non-coding RNA activated by DNA damage (NORAD) on atherosclerosis in CAD remains unclear. The primary aim of this study was to investigate the effect of lncRNA NORAD on vascular endothelial cell injury and atherosclerosis. Here, ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE(–/–) mice were utilized as in vitro and in vivo models. The present study found that lncRNA NORAD expression was increased in ox-LDL-treated HUVECs and thoracic aorta of atherosclerotic mice, and knockdown of lncRNA NORAD alleviated vascular endothelial cell injury and atherosclerosis development in vitro and in vivo. Knockdown of lncRNA NORAD aggravated ox-LDL-reduced or atherosclerosis-decreased vascular endothelial growth factor (VEGF) expression in HUVECs and thoracic aorta of mice to ameliorate vascular endothelial cell injury and atherosclerosis development. Moreover, nucleus lncRNA NORAD suppressed VEGF gene transcription through enhancing H3K9 deacetylation via recruiting HDAC6 to the VEGF gene promoter in ox-LDL-treated HUVECs. In addition, VEGF reduced FUS (FUS RNA binding protein) expression by a negative feedback regulation in HUVECs. In summary, lncRNA NORAD enhanced vascular endothelial cell injury and atherosclerosis through suppressing VEGF gene transcription via enhancing H3K9 deacetylation by recruiting HDAC6. The findings could facilitate discovering novel diagnostic markers and therapeutic targets for CAD. |
format | Online Article Text |
id | pubmed-8301222 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-83012222021-07-24 LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 Kai, Huihua Wu, Qiyong Yin, Ruohan Tang, Xiaoqiang Shi, Haifeng Wang, Tao Zhang, Ming Pan, Changjie Front Cell Dev Biol Cell and Developmental Biology Coronary artery disease (CAD) is a major atherosclerotic cardiovascular disease and the leading cause of mortality globally. Long non-coding RNAs (lncRNAs) play crucial roles in CAD development. To date, the effect of lncRNA non-coding RNA activated by DNA damage (NORAD) on atherosclerosis in CAD remains unclear. The primary aim of this study was to investigate the effect of lncRNA NORAD on vascular endothelial cell injury and atherosclerosis. Here, ox-LDL-treated human umbilical vein endothelial cells (HUVECs) and high-fat-diet (HFD)-fed ApoE(–/–) mice were utilized as in vitro and in vivo models. The present study found that lncRNA NORAD expression was increased in ox-LDL-treated HUVECs and thoracic aorta of atherosclerotic mice, and knockdown of lncRNA NORAD alleviated vascular endothelial cell injury and atherosclerosis development in vitro and in vivo. Knockdown of lncRNA NORAD aggravated ox-LDL-reduced or atherosclerosis-decreased vascular endothelial growth factor (VEGF) expression in HUVECs and thoracic aorta of mice to ameliorate vascular endothelial cell injury and atherosclerosis development. Moreover, nucleus lncRNA NORAD suppressed VEGF gene transcription through enhancing H3K9 deacetylation via recruiting HDAC6 to the VEGF gene promoter in ox-LDL-treated HUVECs. In addition, VEGF reduced FUS (FUS RNA binding protein) expression by a negative feedback regulation in HUVECs. In summary, lncRNA NORAD enhanced vascular endothelial cell injury and atherosclerosis through suppressing VEGF gene transcription via enhancing H3K9 deacetylation by recruiting HDAC6. The findings could facilitate discovering novel diagnostic markers and therapeutic targets for CAD. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8301222/ /pubmed/34307380 http://dx.doi.org/10.3389/fcell.2021.701628 Text en Copyright © 2021 Kai, Wu, Yin, Tang, Shi, Wang, Zhang and Pan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cell and Developmental Biology Kai, Huihua Wu, Qiyong Yin, Ruohan Tang, Xiaoqiang Shi, Haifeng Wang, Tao Zhang, Ming Pan, Changjie LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title | LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title_full | LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title_fullStr | LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title_full_unstemmed | LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title_short | LncRNA NORAD Promotes Vascular Endothelial Cell Injury and Atherosclerosis Through Suppressing VEGF Gene Transcription via Enhancing H3K9 Deacetylation by Recruiting HDAC6 |
title_sort | lncrna norad promotes vascular endothelial cell injury and atherosclerosis through suppressing vegf gene transcription via enhancing h3k9 deacetylation by recruiting hdac6 |
topic | Cell and Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301222/ https://www.ncbi.nlm.nih.gov/pubmed/34307380 http://dx.doi.org/10.3389/fcell.2021.701628 |
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