ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Telomerase therapy attenuates cardiotoxic effects of doxorubicin.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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39 citing papers in PubMed, 60 citations in OpenAlex.
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- Senescence modulated cardiac repair with pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2026Article
- Neuregulin-1β Mitigates Doxorubicin-Induced Cardiotoxicity viaInternational journal of molecular sciences · 2026Article
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- SARS-CoV-2-infected cardiomyocytes exhibit upregulated necroptosis, but no evidence of mitochondrial permeability transition.Journal of molecular and cellular cardiology plus · 2026Article
- Telomerase mRNA therapy protects human skin against radiation-induced DNA damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Telomerase modRNA Offers a Novel RNA-Based Approach to Treat Human Pulmonary Fibrosis.Aging cell · 2025Article
- Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.Journal of clinical immunology · 2025Article
- A circular RNA derived from the ryanodine receptor 2 locus controls cardiac hypertrophy and calcium handling.Cellular and molecular life sciences : CMLS · 2025Article
- Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.Molecular cancer · 2025Review
- Development of a microarray based telomerase binding assay reveals unusual binding of a cytochalasin derivative.Scientific reports · 2025Article
- 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
- Effect of chemotherapy and different chemotherapeutic regimens on electrocardiographic parameters in breast cancer women: a retrospective and within-subject longitudinal study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Article
- Engineering cardiology with miniature hearts.Materials today. Bio · 2025Review
- Telomere Length Is Associated With Adverse Atrial Remodeling in Patients With Atrial Fibrillation.Journal of the American Heart Association · 2025Article
- Gene Therapy for Skin Aging.Current gene therapy · 2025Review
- Neoadjuvant chemotherapy and perioperative cardiotoxicity.Journal of anesthesia and translational medicine · 2024Review
- α-Bisabolol: A Dietary Sesquiterpene that Attenuates Apoptotic and Nonapoptotic Cell Death Pathways by Regulating the Mitochondrial Biogenesis and Endoplasmic Reticulum Stress-Hippo Signaling Axis in Doxorubicin-Induced Acute Cardiotoxicity in Rats.ACS pharmacology & translational science · 2024Article
- Cardiovascular Toxicity in Cancer Therapy: Protecting the Heart while Combating Cancer.Current cardiology reports · 2024Review
- Is There a Mitochondrial Protection via Remote Ischemic Conditioning in Settings of Anticancer Therapy Cardiotoxicity?Current heart failure reports · 2024Review
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13 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Doxorubicin is one of the most potent chemotherapeutic agents. However, its clinical use is restricted due to the severe risk of cardiotoxicity, partially attributed to elevated production of reactive oxygen species (ROS). Telomerase canonically maintains telomeres during cell division but is silenced in adult hearts. In non-dividing cells such as cardiomyocytes, telomerase confers pro-survival traits, likely owing to the detoxification of ROS. Therefore, we hypothesized that pharmacological overexpression of telomerase may be used as a therapeutic strategy for the prevention of doxorubicin-induced cardiotoxicity. We used adeno-associated virus (AAV)-mediated gene therapy for long-term expression of telomerase in in vitro and in vivo models of doxorubicin-induced cardiotoxicity. Overexpression of telomerase protected the heart from doxorubicin-mediated apoptosis and rescued cardiac function, which was accompanied by preserved cardiomyocyte size. At the mechanistic level, we observed altered mitochondrial morphology and dynamics in response to telomerase expression. Complementary in vitro experiments confirmed the anti-apoptotic effects of telomerase overexpression in human induced pluripotent stem cell-derived cardiomyocytes after doxorubicin treatment. Strikingly, elevated levels of telomerase translocated to the mitochondria upon doxorubicin treatment, which helped to maintain mitochondrial function. Thus, telomerase gene therapy could be a novel preventive strategy for cardiotoxicity by chemotherapy agents such as the anthracyclines.
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