ArticleThe Journal of clinical investigation2007
The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 140 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
140 citing papers in PubMed, 255 citations in OpenAlex.
- Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans.American journal of physiology. Heart and circulatory physiology · 2009Trial
- Therapeutic effect of Fuzheng Yixin decoction on cardiac insufficiencythe soluble guanylyl cyclase-cyclic guanosine monophosphate-protein kinase G pathway in a doxorubicin-induced dilated cardiomyopathy rat model.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Article
- Article
- THC and CBD Induce Heme Oxygenase-1-Dependent Cell Death and Trigger Mitochondrial Dysfunction in Human Melanoma and Cutaneous Squamous Cell Carcinoma Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- Mitochondrial transfer from adipose-derived regenerative cells contributes therapeutic angiogenesis in a murine hindlimb ischemia model.Angiogenesis · 2025Article
- Streptozotocin-induced hyperglycemia unmasks cardiotoxicity induced by doxorubicin.Scientific reports · 2025Article
- New insights into mitochondrial quality control in anthracycline-induced cardiotoxicity: molecular mechanisms, therapeutic targets, and natural products.International journal of biological sciences · 2025Review
- Evolution of Theories on Doxorubicin-Induced Late Cardiotoxicity-Role of Topoisomerase.International journal of molecular sciences · 2024Review
- Metal-Free CO Prodrugs Activated by Molecular Oxygen Protect against Doxorubicin-Induced Cardiomyopathy in Mice.Journal of medicinal chemistry · 2024Article
- Cardiac Atrophy, Dysfunction, and Metabolic Impairments: A Cancer-Induced Cardiomyopathy Phenotype.The American journal of pathology · 2024Article
- Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.Journal of the American Heart Association · 2024Article
- Deficiency of heme oxygenase 1a causes detrimental effects on cardiac function.Journal of cellular and molecular medicine · 2024Article
- TBC1D15 deficiency protects against doxorubicin cardiotoxicityActa pharmaceutica Sinica. B · 2023Article
- Water Extract ofInternational journal of molecular sciences · 2023Article
- A Thia-Analogous IndirubinCells · 2023Article
- An ischemic area-targeting, peroxynitrite-responsive, biomimetic carbon monoxide nanogenerator for preventing myocardial ischemia-reperfusion injury.Bioactive materials · 2023Article
- Clinical Applications for Gasotransmitters in the Cardiovascular System: Are We There Yet?International journal of molecular sciences · 2023Review
- Carboxyhemoglobin (COHb): Unavoidable Bystander or Protective Player?Antioxidants (Basel, Switzerland) · 2023Review
- Essential Amino Acids-Rich Diet Increases Cardiomyocytes Protection in Doxorubicin-Treated Mice.Nutrients · 2023Article
80 more citing papers are in PubMed but not listed here.
Corrections and comments
- Retracted
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The clinical utility of anthracycline anticancer agents, especially doxorubicin, is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse heart fails to upregulate the nuclear program for mitochondrial biogenesis and its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive wall stress and fibrosis. Furthermore, we exploited recent evidence that mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial pathology was averted by periodic CO inhalation, which restored mitochondrial biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis-inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis.
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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.