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.
Conclusion
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.
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 14-3-3γ 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.