2. Academic Validation
  3. BACH1 deficiency prevents neointima formation and maintains the differentiated phenotype of vascular smooth muscle cells by regulating chromatin accessibility

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

  • Nucleic Acids Res. 2023 Mar 2;gkad120. doi: 10.1093/nar/gkad120.
Jieyu Guo 1,  Jingjing Qiu 2,  Mengping Jia 1,  Qinhan Li 1,  Xiangxiang Wei 1,  Liliang Li 3,  Qi Pan 1,  Jiayu Jin 1,  Fei Ge 1,  Siyu Ma 1,  Yunquan He 1,  Jiayi Lin 1,  Yongbo Li 1,  Jinghua Ma 1,  Nan Jiang 1,  Xiuling Zhi 1,  Lindi Jiang 1,  Jianyi Zhang 4,  Elena Osto 5,  Qing Jing 2,  Xinhong Wang 1,  Dan Meng 1
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
  • 2 CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institutes of Nutrition and Health, Innovation Center for Intervention of Chronic Disease and Promotion of Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
  • 3 Department of forensic medicine, School of basic medical sciences, Fudan University, Shanghai 200032, China.
  • 4 Department of Biomedical Engineering, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
  • 5 University and University Hospital Zurich, Institute of Clinical Chemistry and Swiss Federal Institute of Technology, Laboratory of Translational Nutrition Biology, Zurich, CH 8952, Switzerland.
PMID: 36864760 DOI: 10.1093/nar/gkad120
Abstract

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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