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BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility

The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Th...

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Autores principales: Guo, Jieyu, Qiu, Jingjing, Jia, Mengping, Li, Qinhan, Wei, Xiangxiang, Li, Liliang, Pan, Qi, Jin, Jiayu, Ge, Fei, Ma, Siyu, He, Yunquan, Lin, Jiayi, Li, Yongbo, Ma, Jinghua, Jiang, Nan, Zhi, Xiuling, Jiang, Lindi, Zhang, Jianyi, Osto, Elena, Jing, Qing, Wang, Xinhong, Meng, Dan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201429/
https://www.ncbi.nlm.nih.gov/pubmed/36864760
http://dx.doi.org/10.1093/nar/gkad120
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author Guo, Jieyu
Qiu, Jingjing
Jia, Mengping
Li, Qinhan
Wei, Xiangxiang
Li, Liliang
Pan, Qi
Jin, Jiayu
Ge, Fei
Ma, Siyu
He, Yunquan
Lin, Jiayi
Li, Yongbo
Ma, Jinghua
Jiang, Nan
Zhi, Xiuling
Jiang, Lindi
Zhang, Jianyi
Osto, Elena
Jing, Qing
Wang, Xinhong
Meng, Dan
author_facet Guo, Jieyu
Qiu, Jingjing
Jia, Mengping
Li, Qinhan
Wei, Xiangxiang
Li, Liliang
Pan, Qi
Jin, Jiayu
Ge, Fei
Ma, Siyu
He, Yunquan
Lin, Jiayi
Li, Yongbo
Ma, Jinghua
Jiang, Nan
Zhi, Xiuling
Jiang, Lindi
Zhang, Jianyi
Osto, Elena
Jing, Qing
Wang, Xinhong
Meng, Dan
author_sort Guo, Jieyu
collection PubMed
description The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1.
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spelling pubmed-102014292023-05-23 BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility Guo, Jieyu Qiu, Jingjing Jia, Mengping Li, Qinhan Wei, Xiangxiang Li, Liliang Pan, Qi Jin, Jiayu Ge, Fei Ma, Siyu He, Yunquan Lin, Jiayi Li, Yongbo Ma, Jinghua Jiang, Nan Zhi, Xiuling Jiang, Lindi Zhang, Jianyi Osto, Elena Jing, Qing Wang, Xinhong Meng, Dan Nucleic Acids Res Gene regulation, Chromatin and Epigenetics The transcription factor BTB and CNC homology 1(BACH1) has been linked to coronary artery disease risk by human genome-wide association studies, but little is known about the role of BACH1 in vascular smooth muscle cell (VSMC) phenotype switching and neointima formation following vascular injury. Therefore, this study aims to explore the role of BACH1 in vascular remodeling and its underlying mechanisms. BACH1 was highly expressed in human atherosclerotic plaques and has high transcriptional factor activity in VSMCs of human atherosclerotic arteries. VSMC-specific loss of Bach1 in mice inhibited the transformation of VSMC from contractile to synthetic phenotype and VSMC proliferation and attenuated the neointimal hyperplasia induced by wire injury. Mechanistically, BACH1 suppressed chromatin accessibility at the promoters of VSMC marker genes via recruiting histone methyltransferase G9a and cofactor YAP and maintaining the H3K9me2 state, thereby repressing VSMC marker genes expression in human aortic smooth muscle cells (HASMCs). BACH1-induced repression of VSMC marker genes was abolished by the silencing of G9a or YAP. Thus, these findings demonstrate a crucial regulatory role of BACH1 in VSMC phenotypic transition and vascular homeostasis and shed light on potential future protective vascular disease intervention via manipulation of BACH1. Oxford University Press 2023-03-02 /pmc/articles/PMC10201429/ /pubmed/36864760 http://dx.doi.org/10.1093/nar/gkad120 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Guo, Jieyu
Qiu, Jingjing
Jia, Mengping
Li, Qinhan
Wei, Xiangxiang
Li, Liliang
Pan, Qi
Jin, Jiayu
Ge, Fei
Ma, Siyu
He, Yunquan
Lin, Jiayi
Li, Yongbo
Ma, Jinghua
Jiang, Nan
Zhi, Xiuling
Jiang, Lindi
Zhang, Jianyi
Osto, Elena
Jing, Qing
Wang, Xinhong
Meng, Dan
BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title_full BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title_fullStr BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title_full_unstemmed BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title_short BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
title_sort bach1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10201429/
https://www.ncbi.nlm.nih.gov/pubmed/36864760
http://dx.doi.org/10.1093/nar/gkad120
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