PMID- 36473288
OWN - NLM
STAT- MEDLINE
DCOM- 20230124
LR  - 20230814
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Print)
IS  - 0022-2828 (Linking)
VI  - 174
DP  - 2023 Jan
TI  - Adenosine kinase promotes post-infarction cardiac repair by epigenetically 
      maintaining reparative macrophage phenotype.
PG  - 88-100
LID - S0022-2828(22)00567-3 [pii]
LID - 10.1016/j.yjmcc.2022.11.007 [doi]
AB  - Pro-inflammatory and reparative macrophages are crucial in clearing necrotic 
      myocardium and promoting cardiac repair after myocardial infarction (MI), 
      respectively. Extracellular adenosine has been demonstrated to modulate 
      macrophage polarization through adenosine receptors. However, the role of 
      intracellular adenosine in macrophage polarization has not been explored and 
      adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine 
      levels. Here, we aimed to elucidate the role of ADK in macrophage polarization 
      and its subsequent impact on MI. We demonstrated that ADK was upregulated in bone 
      marrow-derived macrophages (BMDMs) after IL-4 treatment and was highly expressed 
      in the infarct area at day 7 post-MI, especially in macrophages. Compared with 
      wild-type mice, myeloid-specific Adk knockout mice showed increased infarct size, 
      limited myofibroblast differentiation, reduced collagen deposition and more 
      severe cardiac dysfunction after MI, which was related to impaired reparative 
      macrophage phenotype in MI tissue. We found that ADK deletion or inhibition 
      significantly decreased the expression of reparative genes, such as Arg1, Ym1, 
      Fizz1, and Cd206 in BMDMs after IL-4 treatment. The increased intracellular 
      adenosine due to Adk deletion inhibited transmethylation reactions and decreased 
      the trimethylation of H3K4 in BMDMs after IL-4 treatment. Mechanistically, we 
      demonstrated that Adk deletion suppressed reparative macrophage phenotype through 
      decreased IRF4 expression, which resulted from reduced levels of H3K4me3 on the 
      Irf4 promotor. Together, our study reveals that ADK exerts a protective effect 
      against MI by promoting reparative macrophage polarization through epigenetic 
      mechanisms.
CI  - Copyright (c) 2022. Published by Elsevier Ltd.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China; The First Affiliated 
      Hospital, Jinan University, Guangzhou 510632, China.
FAU - Wang, Caiping
AU  - Wang C
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China.
FAU - Wang, Rongning
AU  - Wang R
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China.
FAU - Xu, Jiean
AU  - Xu J
AD  - State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical 
      Genomics, School of Chemical Biology and Biotechnology, Peking University 
      Shenzhen Graduate School, Shenzhen 518055, China.
FAU - Wang, Zhefeng
AU  - Wang Z
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China; The First Affiliated 
      Hospital, Jinan University, Guangzhou 510632, China.
FAU - Yan, Jianlong
AU  - Yan J
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China.
FAU - Cai, Yongfeng
AU  - Cai Y
AD  - State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical 
      Genomics, School of Chemical Biology and Biotechnology, Peking University 
      Shenzhen Graduate School, Shenzhen 518055, China.
FAU - Li, Liangping
AU  - Li L
AD  - The First Affiliated Hospital, Jinan University, Guangzhou 510632, China; 
      Institute of Clinical Oncology, The First Affiliated Hospital, Jinan University, 
      Guangzhou 510632, China.
FAU - Huo, Yuqing
AU  - Huo Y
AD  - Vascular Biology Center, Department of Cellular Biology and Anatomy, Medical 
      College of Georgia, Augusta University, GA 30912, United States.
FAU - Dong, Shaohong
AU  - Dong S
AD  - Department of Cardiology, The Second Clinical Medical College, Jinan University 
      (Shenzhen People's Hospital), Shenzhen 518020, China. Electronic address: 
      dshszph@163.com.
LA  - eng
GR  - R01 EY030500/EY/NEI NIH HHS/United States
PT  - Journal Article
DEP - 20221205
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - EC 2.7.1.20 (Adenosine Kinase)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Adenosine Kinase/genetics/metabolism
MH  - Interleukin-4/genetics
MH  - Macrophages/metabolism
MH  - *Myocardial Infarction/metabolism
MH  - Myocardium/metabolism
MH  - Phenotype
MH  - Mice, Knockout
MH  - Mice, Inbred C57BL
PMC - PMC10420407
MID - NIHMS1920699
OTO - NOTNLM
OT  - Adenosine kinase
OT  - Cardiac repair
OT  - Histone methylation
OT  - Macrophage polarization
OT  - Myocardial infarction
EDAT- 2022/12/07 06:00
MHDA- 2023/01/25 06:00
PMCR- 2023/08/11
CRDT- 2022/12/06 18:15
PHST- 2022/04/03 00:00 [received]
PHST- 2022/11/19 00:00 [revised]
PHST- 2022/11/23 00:00 [accepted]
PHST- 2022/12/07 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2022/12/06 18:15 [entrez]
PHST- 2023/08/11 00:00 [pmc-release]
AID - S0022-2828(22)00567-3 [pii]
AID - 10.1016/j.yjmcc.2022.11.007 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2023 Jan;174:88-100. doi: 10.1016/j.yjmcc.2022.11.007. Epub 
      2022 Dec 5.