Interferon-regulatory factor-1 boosts bevacizumab cardiotoxicity by the vascular endothelial growth factor A/14-3-3γ axis.

14-3-3γ Bevacizumab Interferon-regulatory factor-1 Myocardial injury VEGFA

Journal

ESC heart failure
ISSN: 2055-5822
Titre abrégé: ESC Heart Fail
Pays: England
ID NLM: 101669191

Informations de publication

Date de publication:
17 Jan 2024
Historique:
revised: 27 09 2023
received: 30 08 2022
accepted: 05 12 2023
medline: 18 1 2024
pubmed: 18 1 2024
entrez: 18 1 2024
Statut: aheadofprint

Résumé

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. 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 14-3-3γ 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 14-3-3γ reversing the effects of IRF1 knockdown on the cell viability and apoptosis of BVZ-treated HL-1 cells. 14-3-3γ 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/14-3-3γ axis. The IRF1-mediated VEGFA/14-3-3γ signalling pathway promotes BVZ-induced myocardial injury. Our study provides evidence for potentially new target genes for the treatment of myocardial injury.

Identifiants

pubmed: 38234115
doi: 10.1002/ehf2.14640
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : National Natural Science Foundation of China
ID : 82060679
Organisme : Jiangxi Provincial Health Department Project
ID : SKJP220212447

Informations de copyright

© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

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Auteurs

Xuan-Ying Chen (XY)

Department of Pharmacy, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.

Meng-Qi Xie (MQ)

Department of Pharmacology, School of Pharmacy, Nanchang University, Nanchang, P. R. China.

Wei-Lin Huang (WL)

Department of Cardiovascular, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.

Wen-Juan Li (WJ)

State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang, P. R. China.

Yan-Ni Lv (YN)

Department of Pharmacy, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.

Xiao-Ping Peng (XP)

Department of Cardiovascular, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, P. R. China.

Classifications MeSH