ArticleEuropean journal of heart failure2014
Ageing is a risk factor in imatinib mesylate cardiotoxicity.
Article in European journal of heart failure, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Evaluating the use of rodents as in vitro, in vivo and ex vivo experimental models for the assessment of tyrosine kinase inhibitor-induced cardiotoxicity: a systematic review.Archives of toxicology · 2025Pooled it
- GATA4-overexpressing BMSCs-derived exosome regulation of myocardial infarction in mice by key miRNA and apoptosis gene CLU.European journal of medical research · 2026Article
- Targeting Inflammation: Cytosporone B Modulates Imatinib-Driven Biochemical Alterations in Rat Heart.International journal of molecular sciences · 2025Article
- Cardiotoxicity of small-molecule kinase inhibitors in cancer therapy.Experimental hematology & oncology · 2025Review
- MEK inhibitors: a promising targeted therapy for cardiovascular disease.Frontiers in cardiovascular medicine · 2024Review
- Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies.Cardiovascular toxicology · 2023Review
- Cardiotoxicity of Selected Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Renal Cell Carcinoma.Biomedicines · 2023Review
- Induction of autophagy has protective roles in imatinib-induced cardiotoxicity.Toxicology reports · 2021Article
- Cardiotoxicity of Novel Targeted Hematological Therapies.Life (Basel, Switzerland) · 2020Review
- Metabolic Plasticity Is an Essential Requirement of Acquired Tyrosine Kinase Inhibitor Resistance in Chronic Myeloid Leukemia.Cancers · 2020Article
- Deacetylase-independent function of SIRT6 couples GATA4 transcription factor and epigenetic activation against cardiomyocyte apoptosis.Nucleic acids research · 2020Article
- Molecular Mechanisms of Cardiomyocyte Death in Drug-Induced Cardiotoxicity.Frontiers in cell and developmental biology · 2020Review
- Pazopanib for renal cell carcinoma leads to elevated mean arterial pressures in a murine model.Clinical and experimental hypertension (New York, N.Y. : 1993) · 2018Article
- Imatinib increases oxygen delivery in extracellular matrix-rich but not in matrix-poor experimental carcinoma.Journal of translational medicine · 2017Article
- miR-155 effectively induces apoptosis in K562 Philadelphia positive cell line through upregulation of p27kip1.BioImpacts : BI · 2017Article
- Assessment of pazopanib-related hypertension, cardiac dysfunction and identification of clinical risk factors for their development.Cardio-oncology (London, England) · 2017Article
- Drug-induced mitochondrial dysfunction and cardiotoxicity.American journal of physiology. Heart and circulatory physiology · 2015Review
- Delivery as nanoparticles reduces imatinib mesylate-induced cardiotoxicity and improves anticancer activity.International journal of nanomedicine · 2015Article
- Caspase-1 cleavage of transcription factor GATA4 and regulation of cardiac cell fate.Cell death & disease · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
aimsChemotherapy-induced heart failure is increasingly recognized as a major clinical challenge. Cardiotoxicity of imatinib mesylate, a highly selective and effective anticancer drug belonging to the new class of tyrosine kinase inhibitors, is being reported in patients, some progressing to congestive heart failure. This represents an unanticipated challenge that could limit effective drug use. Understanding the mechanisms and risk factors of imatinib mesylate cardiotoxicity is crucial for prevention of cardiovascular complications in cancer patients. METHODS AND
resultsWe used genetically engineered mice and primary rat neonatal cardiomyocytes to analyse the action of imatinib on the heart. We found that treatment with imatinib (200 mg/kg/day for 5 weeks) leads to mitochondrial-dependent myocyte loss and cardiac dysfunction, as confirmed by electron microscopy, RNA analysis, and echocardiography. Imatinib cardiotoxicity was more severe in older mice, in part due to an age-dependent increase in oxidative stress. Mechanistically, depletion of the transcription factor GATA4 resulting in decreased levels of its prosurvival targets Bcl-2 and Bcl-XL was an underlying cause of imatinib toxicity. Consistent with this, GATA4 haploinsufficient mice were more susceptible to imatinib, and myocyte-specific up-regulation of GATA4 or Bcl-2 protected against drug-induced cardiotoxicity.
conclusionThe results indicate that imatinib action on the heart targets cardiomyocytes and involves mitochondrial impairment and cell death that can be further aggravated by oxidative stress. This in turn offers a possible explanation for the current conflicting data regarding imatinib cardiotoxicity in cancer patients and suggests that cardiac monitoring of older patients receiving imatinib therapy may be especially warranted.
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