PMID- 38234115
OWN - NLM
STAT- MEDLINE
DCOM- 20240328
LR  - 20240329
IS  - 2055-5822 (Electronic)
IS  - 2055-5822 (Linking)
VI  - 11
IP  - 2
DP  - 2024 Apr
TI  - Interferon-regulatory factor-1 boosts bevacizumab cardiotoxicity by the vascular 
      endothelial growth factor A/14-3-3gamma axis.
PG  - 986-1000
LID - 10.1002/ehf2.14640 [doi]
AB  - AIM: Myocardial injury is a significant cause of death. This study investigated 
      the role and underlying mechanism of interferon-regulatory factor-1 (IRF1) in 
      bevacizumab (BVZ)-induced cardiomyocyte injury. METHODS AND RESULTS: HL-1 cells 
      and C57BL/6 mice receiving BVZ treatment were used to establish in vitro and in 
      vivo models of myocardial injury. The relationship between VEGFA and 14-3-3gamma was 
      verified through co-immunoprecipitation and Glutathione S Transferase (GST) 
      pull-down assay. Cell viability and apoptosis were analysed by MTT, propidium 
      iodide (PI) staining and flow cytometry. The release of lactate dehydrogenase 
      (LDH), cardiac troponins T (cTnT), and creatine kinase MB (CK-MB) was measured 
      using the enzyme linked immunosorbent assay. The effects of knocking down IRF1 on 
      BVZ-induced mice were analysed in vivo. IRF1 levels were increased in BVZ-treated 
      HL-1 cells. BVZ treatment induced apoptosis, inhibited cell viability, and 
      promoted the release of LDH, cTnT, and CK-MB. IRF1 silencing suppressed 
      BVZ-induced myocardial injury, whereas IRF1 overexpression had the opposite 
      effect. IRF1 regulated VEGFA expression by binding to its promoter, with the 
      depletion of VEGFA or 14-3-3gamma reversing the effects of IRF1 knockdown on the cell 
      viability and apoptosis of BVZ-treated HL-1 cells. 14-3-3gamma overexpression 
      promoted cell proliferation, inhibited apoptosis, and reduced the release of LDH, 
      cTnT, and CK-MB, thereby alleviating BVZ-induced HL-1 cell damage. In vivo, IRF1 
      silencing alleviated BVZ-induced cardiomyocyte injury by regulating the 
      VEGFA/14-3-3gamma axis. CONCLUSION: The IRF1-mediated VEGFA/14-3-3gamma signalling 
      pathway promotes BVZ-induced myocardial injury. Our study provides evidence for 
      potentially new target genes for the treatment of myocardial injury.
CI  - (c) 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on 
      behalf of European Society of Cardiology.
FAU - Chen, Xuan-Ying
AU  - Chen XY
AD  - Department of Pharmacy, The 1st Affiliated Hospital, Jiangxi Medical College, 
      Nanchang University, Nanchang, P. R. China.
FAU - Xie, Meng-Qi
AU  - Xie MQ
AD  - Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, P. 
      R. China.
FAU - Huang, Wei-Lin
AU  - Huang WL
AD  - Department of Cardiovascular, The 1st Affiliated Hospital, Jiangxi Medical 
      College, Nanchang University, Nanchang, P. R. China.
FAU - Li, Wen-Juan
AU  - Li WJ
AD  - State Key Laboratory of Food Science and Technology, Nanchang University, 
      Nanchang, P. R. China.
FAU - Lv, Yan-Ni
AU  - Lv YN
AD  - Department of Pharmacy, The 1st Affiliated Hospital, Jiangxi Medical College, 
      Nanchang University, Nanchang, P. R. China.
FAU - Peng, Xiao-Ping
AU  - Peng XP
AD  - Department of Cardiovascular, The 1st Affiliated Hospital, Jiangxi Medical 
      College, Nanchang University, Nanchang, P. R. China.
LA  - eng
GR  - 82060679/National Natural Science Foundation of China/
GR  - SKJP220212447/Jiangxi Provincial Health Department Project/
PT  - Journal Article
DEP - 20240117
PL  - England
TA  - ESC Heart Fail
JT  - ESC heart failure
JID - 101669191
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Mice
MH  - Animals
MH  - Bevacizumab/pharmacology
MH  - *Vascular Endothelial Growth Factor A
MH  - *Cardiotoxicity
MH  - Mice, Inbred C57BL
MH  - Interferons
PMC - PMC10966242
OTO - NOTNLM
OT  - 14-3-3gamma
OT  - Bevacizumab
OT  - Interferon-regulatory factor-1
OT  - Myocardial injury
OT  - VEGFA
COIS- The authors declare that they have no conflict of interest.
EDAT- 2024/01/18 06:42
MHDA- 2024/03/28 06:45
PMCR- 2024/01/17
CRDT- 2024/01/18 02:03
PHST- 2023/09/27 00:00 [revised]
PHST- 2022/08/30 00:00 [received]
PHST- 2023/12/05 00:00 [accepted]
PHST- 2024/03/28 06:45 [medline]
PHST- 2024/01/18 06:42 [pubmed]
PHST- 2024/01/18 02:03 [entrez]
PHST- 2024/01/17 00:00 [pmc-release]
AID - EHF214640 [pii]
AID - 10.1002/ehf2.14640 [doi]
PST - ppublish
SO  - ESC Heart Fail. 2024 Apr;11(2):986-1000. doi: 10.1002/ehf2.14640. Epub 2024 Jan 
      17.