ArticleAmerican journal of physiology. Cell physiology2020
Accelerated cardiomyocyte senescence contributes to late-onset doxorubicin-induced cardiotoxicity.
Article in American journal of physiology. Cell physiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 121 citations in OpenAlex.
- Mechanisms of Doxorubicin-Induced Cardiac Senescence and Potential Therapeutic Strategies.Biomolecules · 2026Review
- Breaking senescence restriction: MAFK-AREG axis promotes NSCLC cells to resist doxorubicin.Oncology letters · 2026Article
- Mitochondrial-Targeted SS-31 Attenuates the Doxorubicin-Induced Cardiomyoblast H9C2 Cell Senescence.Biology · 2026Article
- Review
- Safety and Treatment Efficacy of Systemic, Locoregional, and Nanoparticle Encapsulated Anthracycline Chemotherapy: Insights Into Cardiotoxicity.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- RNAi-mediated p38δ silencing mitigates anthracycline cardiotoxicity in female mice.American journal of physiology. Heart and circulatory physiology · 2026Article
- Doxorubicin-Induced Cardiac Remodeling: Mechanisms and Mitigation Strategies.Cardiovascular drugs and therapy · 2026Review
- Review
- Inhibition of PAI-1 shifts cardiomyocyte fate from senescence toward apoptosis and mitigates doxorubicin-induced cardiotoxicity.Geromedicine · 2026Article
- The role of cellular senescence in cardiovascular disease.Cell death discovery · 2025Review
- Elevation of p53 sensitizes obese kidney to adriamycin-induced aberrant lipid homeostasis via repressing HNF4α-mediated FGF21 sensitivity.Journal of advanced research · 2025Article
- Sendotypes predict worsening renal function in chronic kidney disease patients.Clinical and translational medicine · 2025Article
- NADPH Oxidases in Cancer Therapy-Induced Cardiotoxicity: Mechanisms and Therapeutic Approaches.Cardiovascular toxicology · 2025Review
- Mitochondrial Amount Determines Doxorubicin-Induced Cardiotoxicity in Cardiomyocytes.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Review
- Cannabidiol Ameliorates Doxorubicin-Induced Myocardial Injury via Activating Hippo Pathway.Drug design, development and therapy · 2025Article
- Cancer therapy-related cardiovascular aging: mechanisms, monitoring, and intervention strategies.Frontiers in cardiovascular medicine · 2025Review
- Mechanisms of aging in the cardiovascular system: challenges and opportunities.Frontiers in immunology · 2025Review
- A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence.Cell communication and signaling : CCS · 2024Review
- Losmapimod ameliorates doxorubicin-induced cardiotoxicity through attenuating senescence and inflammatory pathways.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Children surviving cancer and chemotherapy are at risk for adverse health events including heart failure that may be delayed by years. Although the early effects of doxorubicin-induced cardiotoxicity may be attributed to a direct effect on the cardiomyocytes, the mechanisms underlying the delayed or late effects (8-20 yr) are unknown. The goal of this project was to develop a model of late-onset doxorubicin-induced cardiotoxicity to better delineate the underlying pathophysiology responsible. The underlying hypothesis was that doxorubicin-induced "late-onset cardiotoxicity" was the result of mitochondrial dysfunction leading to cell failure and death. Wistar rats, 3-4 wk of age, were randomly assigned to vehicle or doxorubicin injection groups (1-45 mg/kg). Cardiovascular function was unaltered at the lower dosages (1-15 kg/mg), but beginning at 6 mo after injection significant cardiac degradation was observed in the 45 mg/kg group. Doxorubicin significantly increased myocardial mitochondrial DNA (mtDNA) damage. In contrast, in isolated c-kit left ventricular (LV) cells, doxorubicin treatment did not increase mtDNA damage. Biomarkers of senescence within the LV were significantly increased, suggesting accelerated aging of the LV. Doxorubicin also significantly increased LV histamine content suggestive of mast cell activation. With the use of flow cytometry, a significant expansion of the c-kit and stage-specific embryonic antigen 1 cell populations within the LV were concomitant with significant decreases in the circulating peripheral blood population of these cells. These results are consistent with the concept that doxorubicin induced significant damage to the cardiomyocyte population and that although the heart attempted to compensate it eventually succumbed to an inability for self-repair.
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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 Socratic graph.