PMID- 38323308
OWN - NLM
STAT- MEDLINE
DCOM- 20240208
LR  - 20240212
IS  - 1838-7640 (Electronic)
IS  - 1838-7640 (Linking)
VI  - 14
IP  - 3
DP  - 2024
TI  - Single-cell RNA sequencing reveals S100a9(hi) macrophages promote the transition 
      from acute inflammation to fibrotic remodeling after myocardial 
      ischemia‒reperfusion.
PG  - 1241-1259
LID - 10.7150/thno.91180 [doi]
AB  - Rationale: The transition from acute inflammation to fibrosis following 
      myocardial ischemia‒reperfusion (MIR) significantly affects prognosis. 
      Macrophages play a pivotal role in inflammatory damage and repair after MIR. 
      However, the heterogeneity and transformation mechanisms of macrophages during 
      this transition are not well understood. Methods: In this study, we used 
      single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine 
      monocyte-derived macrophages after MIR to investigate macrophage subtypes and 
      their roles in the MIR process. S100a9(-/-) mice were used to establish MIR model 
      to clarify the mechanism of alleviating inflammation and fibrosis after MIR. 
      Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion 
      (MD) in mice subjected to MIR were performed to further examine the role of 
      S100a9(hi) macrophages in MIR. Results: We identified a unique subtype of 
      S100a9(hi) macrophages that originate from monocytes and are involved in acute 
      inflammation and fibrosis. These S100a9(hi) macrophages infiltrate the heart as 
      early as 2 h post-reperfusion and activate the Myd88/NFkappaB/NLRP3 signaling 
      pathway, amplifying inflammatory responses. As the tissue environment shifts from 
      proinflammatory to reparative, S100a9 activates transforming growth factor-beta 
      (Tgf-beta)/p-smad3 signaling. This activation not only induces the transformation of 
      myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the 
      macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific 
      inhibitor could effectively mitigate acute inflammatory damage and halt the 
      progression of fibrosis, including MMT. Conclusion: S100a9(hi) macrophages are a 
      promising therapeutic target for managing the transition from inflammation to 
      fibrosis after MIR.
CI  - (c) The author(s).
FAU - Shen, Shichun
AU  - Shen S
AD  - Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
FAU - Zhang, Meng
AU  - Zhang M
AD  - Department of Cardiology, The Second Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Wang, Xiaohe
AU  - Wang X
AD  - Department of Cardiology, The Second Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Liu, Qiaoling
AU  - Liu Q
AD  - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, 
      United Kingdom.
FAU - Su, Huimin
AU  - Su H
AD  - Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
FAU - Sun, Bingyi
AU  - Sun B
AD  - The First Clinical Medical school of Anhui Medical university, Hefei, China.
FAU - Guo, Zhiqing
AU  - Guo Z
AD  - Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
FAU - Tian, Beiduo
AU  - Tian B
AD  - Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
FAU - Gan, Hong
AU  - Gan H
AD  - Department of Maternal, Child and Adolescent Health, School of Public Health, 
      Anhui Medical University, No 81 Meishan Road, Hefei 230032, Anhui, China.
AD  - MOE Key Laboratory of Population Health Across Life Cycle, Hefei, China.
FAU - Gong, Chen
AU  - Gong C
AD  - Department of Pediatrics, The First Affiliated Hospital of Anhui Medical 
      University, Hefei, China.
FAU - Ma, Likun
AU  - Ma L
AD  - Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life 
      Sciences and Medicine, University of Science and Technology of China, Hefei, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20240120
PL  - Australia
TA  - Theranostics
JT  - Theranostics
JID - 101552395
SB  - IM
MH  - Mice
MH  - Animals
MH  - Macrophages/metabolism
MH  - *Myocardial Reperfusion Injury/pathology
MH  - Fibrosis
MH  - Inflammation/metabolism
MH  - *Coronary Artery Disease/pathology
MH  - Ischemia/pathology
MH  - Reperfusion
MH  - Sequence Analysis, RNA
MH  - Mice, Inbred C57BL
PMC - PMC10845204
OTO - NOTNLM
OT  - S100a9hi macrophages
OT  - cardiac fibrosis
OT  - inflammation
OT  - macrophage-to-myofibroblast transition
OT  - myocardial ischemia-reperfusion injury
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2024/02/07 06:43
MHDA- 2024/02/08 06:43
PMCR- 2024/01/01
CRDT- 2024/02/07 04:19
PHST- 2023/10/16 00:00 [received]
PHST- 2023/12/29 00:00 [accepted]
PHST- 2024/02/08 06:43 [medline]
PHST- 2024/02/07 06:43 [pubmed]
PHST- 2024/02/07 04:19 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - thnov14p1241 [pii]
AID - 10.7150/thno.91180 [doi]
PST - epublish
SO  - Theranostics. 2024 Jan 20;14(3):1241-1259. doi: 10.7150/thno.91180. eCollection 
      2024.