Myeloid BAF60a deficiency alters metabolic homeostasis and exacerbates atherosclerosis

Yang Zhao; Yuhao Liu; Guizhen Zhao; Haocheng Lu; Yaozhong Liu; Chao Xue; Ziyi Chang; Hongyu Liu; Yongjie Deng; Wenying Liang; Huilun Wang; Oren Rom; Minerva T. Garcia-Barrio; Tianqing Zhu; Yanhong Guo; Lin Chang; Jiandie Lin; Y. Eugene Chen; Jifeng Zhang

Cell Reports (Oct 2023)

Myeloid BAF60a deficiency alters metabolic homeostasis and exacerbates atherosclerosis

Yang Zhao,
Yuhao Liu,
Guizhen Zhao,
Haocheng Lu,
Yaozhong Liu,
Chao Xue,
Ziyi Chang,
Hongyu Liu,
Yongjie Deng,
Wenying Liang,
Huilun Wang,
Oren Rom,
Minerva T. Garcia-Barrio,
Tianqing Zhu,
Yanhong Guo,
Lin Chang,
Jiandie Lin,
Y. Eugene Chen,
Jifeng Zhang

Affiliations

Yang Zhao: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Yuhao Liu: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Guizhen Zhao: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Haocheng Lu: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Department of Pharmacology, Southern University of Science and Technology, Shenzhen, Guangdong 518055, China
Yaozhong Liu: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Chao Xue: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Ziyi Chang: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Hongyu Liu: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Yongjie Deng: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Wenying Liang: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Huilun Wang: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Oren Rom: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Department of Pathology and Translational Pathobiology, Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA 71103, USA
Minerva T. Garcia-Barrio: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Tianqing Zhu: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Yanhong Guo: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Lin Chang: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Jiandie Lin: Life Sciences Institute and Department of Cell & Developmental Biology, University of Michigan Medical Center, Ann Arbor, MI 48109, USA
Y. Eugene Chen: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, USA
Jifeng Zhang: Department of Internal Medicine, Cardiovascular Center, University of Michigan Medical Center, Ann Arbor, MI 48109, USA; Corresponding author

Journal volume & issue: Vol. 42, no. 10
p. 113171

Abstract

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Summary: Atherosclerosis, a leading health concern, stems from the dynamic involvement of immune cells in vascular plaques. Despite its significance, the interplay between chromatin remodeling and transcriptional regulation in plaque macrophages is understudied. We discovered the reduced expression of Baf60a, a component of the switch/sucrose non-fermentable (SWI/SNF) chromatin remodeling complex, in macrophages from advanced plaques. Myeloid-specific Baf60a deletion compromised mitochondrial integrity and heightened adhesion, apoptosis, and plaque development. BAF60a preserves mitochondrial energy homeostasis under pro-atherogenic stimuli by retaining nuclear respiratory factor 1 (NRF1) accessibility at critical genes. Overexpression of BAF60a rescued mitochondrial dysfunction in an NRF1-dependent manner. This study illuminates the BAF60a-NRF1 axis as a mitochondrial function modulator in atherosclerosis, proposing the rejuvenation of perturbed chromatin remodeling machinery as a potential therapeutic target.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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