ArticlePloS one2013
Creatine kinase-overexpression improves myocardial energetics, contractile dysfunction and survival in murine doxorubicin cardiotoxicity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Anthracycline cardiotoxicity: role of metabolic vulnerability induced by cardiac pressure overload.European heart journal · 2026Article
- Targeting the Apelin-APJ Axis: A Promising Strategy to Mitigate Anthracycline-Induced Cardiotoxicity.Cardiovascular toxicology · 2026Review
- Maintaining energy provision in the heart: the creatine kinase system in ischaemia-reperfusion injury and chronic heart failure.Clinical science (London, England : 1979) · 2024Review
- Context-dependent roles for ubiquitous mitochondrial creatine kinase CKMT1 in breast cancer progression.Cell reports · 2024Article
- CardiacHeart failure reviews · 2023Review
- Synergistic effect on cardiac energetics by targeting the creatine kinase system: in vivo application of high-resolutionJournal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance · 2023Article
- Cardiovascular Magnetic Resonance Imaging in the Early Detection of Cardiotoxicity Induced by Cancer Therapies.Diagnostics (Basel, Switzerland) · 2022Review
- Mitochondrial Creatine Kinase Attenuates Pathologic Remodeling in Heart Failure.Circulation research · 2022Observational
- Supplementing Soy-Based Diet with Creatine in Rats: Implications for Cardiac Cell Signaling and Response to Doxorubicin.Nutrients · 2022Article
- New Insights in Early Detection of Anticancer Drug-Related Cardiotoxicity Using Perfusion and Metabolic Imaging.Frontiers in cardiovascular medicine · 2022Review
- MiR-199 Aggravates Doxorubicin-Induced Cardiotoxicity by Targeting TAF9b.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Mechanisms and Drug Intervention for Doxorubicin-Induced Cardiotoxicity Based on Mitochondrial Bioenergetics.Oxidative medicine and cellular longevity · 2022Review
- Role of Creatine in the Heart: Health and Disease.Nutrients · 2021Review
- Metabolic Aspects of Anthracycline Cardiotoxicity.Current treatment options in oncology · 2021Review
- The Pitfalls ofFrontiers in physiology · 2021Review
- Mitochondrial CaMKII causes adverse metabolic reprogramming and dilated cardiomyopathy.Nature communications · 2020Article
- Non-invasive investigation of myocardial energetics in cardiac disease usingCardiovascular diagnosis and therapy · 2020Review
- Metabolic Imaging in Cardio-oncology.Journal of cardiovascular translational research · 2020Review
- Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients.Cardiac failure review · 2019Review
- Cardiovascular Magnetic Resonance in the Oncology Patient.JACC. Cardiovascular imaging · 2018Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Doxorubicin (DOX) is a commonly used life-saving antineoplastic agent that also causes dose-dependent cardiotoxicity. Because ATP is absolutely required to sustain normal cardiac contractile function and because impaired ATP synthesis through creatine kinase (CK), the primary myocardial energy reserve reaction, may contribute to contractile dysfunction in heart failure, we hypothesized that impaired CK energy metabolism contributes to DOX-induced cardiotoxicity. We therefore overexpressed the myofibrillar isoform of CK (CK-M) in the heart and determined the energetic, contractile and survival effects of CK-M following weekly DOX (5 mg/kg) administration using in vivo (31)P MRS and (1)H MRI. In control animals, in vivo cardiac energetics were reduced at 7 weeks of DOX protocol and this was followed by a mild but significant reduction in left ventricular ejection fraction (EF) at 8 weeks of DOX, as compared to baseline. At baseline, CK-M overexpression (CK-M-OE) increased rates of ATP synthesis through cardiac CK (CK flux) but did not affect contractile function. Following DOX however, CK-M-OE hearts had better preservation of creatine phosphate and higher CK flux and higher EF as compared to control DOX hearts. Survival after DOX administration was significantly better in CK-M-OE than in control animals (p<0.02). Thus CK-M-OE attenuates the early decline in myocardial high-energy phosphates and contractile function caused by chronic DOX administration and increases survival. These findings suggest that CK impairment plays an energetic and functional role in this DOX-cardiotoxicity model and suggests that metabolic strategies, particularly those targeting CK, offer an appealing new strategy for limiting DOX-associated cardiotoxicity.
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Registered trials
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.