PMID- 37121564
OWN - NLM
STAT- MEDLINE
DCOM- 20230522
LR  - 20230522
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 950
DP  - 2023 Jul 5
TI  - Ergothioneine improves myocardial remodeling and heart function after acute 
      myocardial infarction via S-glutathionylation through the NF-kB dependent 
      Wnt5a-sFlt-1 pathway.
PG  - 175759
LID - S0014-2999(23)00270-4 [pii]
LID - 10.1016/j.ejphar.2023.175759 [doi]
AB  - Myocardial infarction (MI) remains the leading cause of cardiovascular death 
      worldwide. Studies have shown that soluble fms-like tyrosine kinase-1 (sFlt-1) 
      has a harmful effect on the heart after MI. However, ergothioneine (ERG) has been 
      shown to have protective effects in rats with preeclampsia by reducing 
      circulating levels of sFlt-1. In this study, we aimed to investigate the 
      mechanism by which ERG protects the heart after MI in rats. Our results indicate 
      that treatment with 10 mg/kg ERG for 7 days can improve cardiac function as 
      determined by echocardiography. Additionally, ERG can reduce the size of the 
      damaged area, prevent heart remodeling, fibrosis, and reduce cardiomyocyte death 
      after MI. To explain the mechanism behind the cardioprotective effects of ERG, we 
      conducted several experiments. We observed a significant reduction in the 
      expression of monocyte chemoattractant protein-1 (MCP-1), p65, and p-p65 proteins 
      in heart tissues of ERG-treated rats compared to the control group. ELISA results 
      also showed that ERG significantly reduced plasma levels of sFlt-1. Using 
      Glutaredoxin-1 (GLRX) and CD31 immunofluorescence, we found that GLRX was 
      expressed in clusters in the myocardial tissue surrounding the coronary artery, 
      and ERG can reduce the expression of GLRX caused by MI. In vitro experiments 
      using a human coronary artery endothelial cell (HCAEC) hypoxia model confirmed 
      that ERG can reduce the expression of sFlt-1, GLRX, and Wnt5a. These findings 
      suggest that ERG protects the heart from MI damage by reducing 
      s-glutathionylation through the NF-kB-dependent Wnt5a-sFlt-1 pathway.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Duan, Rui
AU  - Duan R
AD  - Department of Cardiology, Xuzhou Central Hospital, Jiangsu, PR China.
FAU - Pan, Haotian
AU  - Pan H
AD  - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu, PR China.
FAU - Li, DongCheng
AU  - Li D
AD  - Department of Cardiology, Huai'an First People's Hospital, Jiangsu, PR China.
FAU - Liao, Shengen
AU  - Liao S
AD  - Department of Cardiology, The First Affiliated Hospital of Nanjing Medical 
      University, Jiangsu, PR China. Electronic address: shengenliao@163.com.
FAU - Han, Bing
AU  - Han B
AD  - Department of Cardiology, Xuzhou Central Hospital, Jiangsu, PR China. Electronic 
      address: hbing777@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230428
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (NF-kappa B)
RN  - BDZ3DQM98W (Ergothioneine)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (WNT5A protein, human)
RN  - 0 (Wnt-5a Protein)
RN  - 0 (Wnt5a protein, rat)
SB  - IM
MH  - Pregnancy
MH  - Female
MH  - Rats
MH  - Humans
MH  - Animals
MH  - NF-kappa B/metabolism
MH  - *Ergothioneine/pharmacology/therapeutic use
MH  - *Myocardial Infarction/metabolism
MH  - Heart
MH  - Myocardium/metabolism
MH  - Receptor Protein-Tyrosine Kinases
MH  - Vascular Endothelial Growth Factor A
MH  - Wnt-5a Protein
OTO - NOTNLM
OT  - Ergothioneine
OT  - Glutaredoxin-1
OT  - Myocardial infarction
OT  - Soluble fms-like tyrosine kinase-1
OT  - Wnt5a
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/05/01 00:42
MHDA- 2023/05/22 06:42
CRDT- 2023/04/30 19:30
PHST- 2022/02/09 00:00 [received]
PHST- 2023/04/27 00:00 [revised]
PHST- 2023/04/28 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2023/05/01 00:42 [pubmed]
PHST- 2023/04/30 19:30 [entrez]
AID - S0014-2999(23)00270-4 [pii]
AID - 10.1016/j.ejphar.2023.175759 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2023 Jul 5;950:175759. doi: 10.1016/j.ejphar.2023.175759. Epub 
      2023 Apr 28.