ArticleAmerican journal of physiology. Heart and circulatory physiology2015
ErbB2 overexpression upregulates antioxidant enzymes, reduces basal levels of reactive oxygen species, and protects against doxorubicin cardiotoxicity.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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61 citing papers in PubMed, 110 citations in OpenAlex.
- Genetic Variability of Antioxidative Mechanisms and Cardiotoxicity after Adjuvant Radiotherapy in HER2-Positive Breast Cancer Patients.Disease markers · 2020Trial
- Cardio-Oncology in Cold Climates: Epidemiological Features, Bidirectional Interaction Mechanisms, and Integrated Management Strategies.Cardiovascular toxicology · 2026Review
- Metabolic phenotypes of doxorubicin-induced cardiotoxicity among patients with breast cancer.Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.European journal of heart failure · 2025Review
- Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update.Journal of cardiovascular development and disease · 2025Review
- Deciphering the roles of cellular and extracellular non-coding RNAs in chemotherapy-induced cardiotoxicity.Molecular and cellular biochemistry · 2025Review
- The Complex Connection Between Myocardial Dysfunction and Cancer Beyond Cardiotoxicity: Shared Risk Factors and Common Molecular Pathways.International journal of molecular sciences · 2024Review
- Article
- Empagliflozin and liraglutide ameliorate HFpEF in mice via augmenting the Erbb4 signaling pathway.Acta pharmacologica Sinica · 2024Article
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- ADPN Regulates Oxidative Stress-Induced Follicular Atresia in Geese by Modulating Granulosa Cell Apoptosis and Autophagy.International journal of molecular sciences · 2024Article
- The Roles of Exosome-Derived microRNAs in Cardiac Fibrosis.Molecules (Basel, Switzerland) · 2024Review
- Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.JACC. CardioOncology · 2024Article
- Anthracycline Toxicity: Light at the End of the Tunnel?Annual review of pharmacology and toxicology · 2024Review
- Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment.Drug design, development and therapy · 2024Review
- Dehydroevodiamine Alleviates Doxorubicin-Induced Cardiomyocyte Injury by Regulating Neuregulin-1/ErbB Signaling.Cardiovascular therapeutics · 2024Article
- Advancements in understanding cardiotoxicity of EGFR- TKIs in non-small cell lung cancer treatment and beyond.Frontiers in pharmacology · 2024Review
- Acetylcholinesterase inhibition protects against trastuzumab-induced cardiotoxicity through reducing multiple programmed cell death pathways.Molecular medicine (Cambridge, Mass.) · 2023Article
- Article
- Mechanisms of trastuzumab induced cardiotoxicity - is exercise a potential treatment?Cardio-oncology (London, England) · 2023Review
1 more citing papers are in PubMed but not listed here.
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12 authors at 3 institutions in 1 country.
Funding
Abstract
Levels of the HER2/ErbB2 protein in the heart are upregulated in some women during breast cancer therapy, and these women are at high risk for developing heart dysfunction after sequential treatment with anti-ErbB2/trastuzumab or doxorubicin. Doxorubicin is known to increase oxidative stress in the heart, and thus we considered the possibility that ErbB2 protein influences the status of cardiac antioxidant defenses in cardiomyocytes. In this study, we measured reactive oxygen species (ROS) in cardiac mitochondria and whole hearts from mice with cardiac-specific overexpression of ErbB2 (ErbB2(tg)) and found that, compared with control mice, high levels of ErbB2 in myocardium result in lower levels of ROS in mitochondria (P = 0.0075) and whole hearts (P = 0.0381). Neonatal cardiomyocytes isolated from ErbB2(tg) hearts have lower ROS levels and less cellular death (P < 0.0001) following doxorubicin treatment. Analyzing antioxidant enzyme levels and activities, we found that ErbB2(tg) hearts have increased levels of glutathione peroxidase 1 (GPx1) protein (P < 0.0001) and GPx activity (P = 0.0031) in addition to increased levels of two known GPx activators, c-Abl (P = 0.0284) and Arg (P < 0.0001). Interestingly, although mitochondrial ROS emission is reduced in the ErbB2(tg) hearts, oxygen consumption rates and complex I activity are similar to control littermates. Compared with these in vivo studies, H9c2 cells transfected with ErbB2 showed less cellular toxicity and produced less ROS (P < 0.0001) after doxorubicin treatment but upregulated GR activity (P = 0.0237) instead of GPx. Our study shows that ErbB2-dependent signaling contributes to antioxidant defenses and suggests a novel mechanism by which anticancer therapies involving ErbB2 antagonists can harm myocardial structure and function.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.