2. Academic Validation
  3. Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation

Macrophage MCT4 inhibition activates reparative genes and protects from atherosclerosis by histone H3 lysine 18 lactylation

  • Cell Rep. 2024 May 28;43(5):114180. doi: 10.1016/j.celrep.2024.114180.
Yunjia Zhang 1,  Hong Jiang 2,  Mengdie Dong 2,  Jiao Min 2,  Xian He 2,  Yongkang Tan 2,  Fuhao Liu 3,  Minghong Chen 2,  Xiang Chen 2,  Quanwen Yin 2,  Longbin Zheng 4,  Yongfeng Shao 5,  Xuesong Li 6,  Hongshan Chen 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, and Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 2 Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 3 Department of Clinical Medicine, Nanjing Medical University Tianyuan Honors School, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
  • 4 Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Department of Anesthesiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu 211112, China.
  • 5 Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: shaoyongfeng@njmu.edu.cn.
  • 6 Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: xuesongli@njmu.edu.cn.
  • 7 Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, and Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, China. Electronic address: hongshanchen@njmu.edu.cn.
PMID: 38733581 DOI: 10.1016/j.celrep.2024.114180
Abstract

Macrophage activation is a hallmark of atherosclerosis, accompanied by a switch in core metabolism from Oxidative Phosphorylation to glycolysis. The crosstalk between metabolic rewiring and histone modifications in macrophages is worthy of further investigation. Here, we find that lactate efflux-associated Monocarboxylate Transporter 4 (MCT4)-mediated histone lactylation is closely related to atherosclerosis. Histone H3 lysine 18 lactylation dependent on MCT4 deficiency activated the transcription of anti-inflammatory genes and tricarboxylic acid cycle genes, resulting in the initiation of local repair and homeostasis. Strikingly, histone lactylation is characteristically involved in the stage-specific local repair process during M1 to M2 transformation, whereas histone methylation and acetylation are not. Gene manipulation and protein hydrolysis-targeted chimerism technology are used to confirm that MCT4 deficiency favors ameliorating atherosclerosis. Therefore, our study shows that macrophage MCT4 deficiency, which links metabolic rewiring and histone modifications, plays a key role in training macrophages to become repair and homeostasis phenotypes.

Keywords

CP: Molecular biology; MCT4; atherosclerosis; histone lactylation; inflammatory; macrophage; tissue repair.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z