ArticleNature2017
Hypoxia induces heart regeneration in adult mice.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05632432 (Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery), which is not on this map. Cited by 418 papers.
What it found
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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.
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.
Autologous Atrial Appendage Micrografts Transplanted During Coronary Artery Bypass Surgery: the AAMS2 Randomized, Double-blinded, and Placebo-controlled Trial
Who cites it
418 citing papers in PubMed, 688 citations in OpenAlex.
- Environmental cues signal through circadian control of sarcomeric gene expression during cardiomyocyte hypertrophy.Epigenetics · 2026Article
- Oxygen physiology and mechanisms of oxygen toxicity: a narrative review.Medical gas research · 2026Review
- A second-generation "hypoxia in a pill" rescues neurodegenerative phenotypes across distinct mouse models.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Multi-omics analysis of early reperfused ischemic heart reveals ERRβ/γ activation protects against acute myocardial infarction injury.Journal of advanced research · 2026Article
- Phosphorescence lifetime microscopy and contrast-enhanced ultrasound imaging revealed strong left-to-right intraventricular shunt in anesthetized Xenopus laevis.The journal of physiological sciences : JPS · 2026Article
- Activation of Glucose-6-Phosphate Dehydrogenase Promotes Cardiomyocyte Cell Cycle.Circulation · 2026Article
- Small-molecule cocktail 2SM promotes heart regeneration via inducing embryonic-like cardiomyocyte state.Cell regeneration (London, England) · 2026Article
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Epigenetic Control of Mammalian Cardiomyocyte Proliferation.Current cardiology reports · 2026Review
- Cardiac regeneration and repair: the emerging mechanisms and therapeutic approaches.Molecular biomedicine · 2026Review
- Hypoxia-mediated epicardial signaling coordinates coronary angiogenesis and myocardial expansion during zebrafish ventricle maturation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Retinol saturase in the mitochondria antagonizes IDH2 and GLUD1 acetylation to mediate heart repair.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- The Metabolic Role of Mitochondria in the Perinatal Cardiac Development and Cardiovascular Diseases.Exploration (Beijing, China) · 2026Review
- Rejuvenating the damaged and aged heart: lessons from development.npj biomedical innovations · 2026Review
- MCPPIR promotes cardiomyocyte proliferation and cardiac repair via o8G oxidation of POC1B mRNA.Cardiovascular research · 2026Article
- Restoration of RBM22 overcomes the transcriptional and epigenetic barriers of cardiomyocyte proliferation for heart regeneration.Nature communications · 2026Article
- Hypoxia Preserves Chromatin Integrity and Delays Cellular Senescence through Epigenetic Regulation.Biomolecules & therapeutics · 2026Review
358 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 5 institutions in 3 countries.
Funding
Abstract
The adult mammalian heart is incapable of regeneration following cardiomyocyte loss, which underpins the lasting and severe effects of cardiomyopathy. Recently, it has become clear that the mammalian heart is not a post-mitotic organ. For example, the neonatal heart is capable of regenerating lost myocardium, and the adult heart is capable of modest self-renewal. In both of these scenarios, cardiomyocyte renewal occurs via the proliferation of pre-existing cardiomyocytes, and is regulated by aerobic-respiration-mediated oxidative DNA damage. Therefore, we reasoned that inhibiting aerobic respiration by inducing systemic hypoxaemia would alleviate oxidative DNA damage, thereby inducing cardiomyocyte proliferation in adult mammals. Here we report that, in mice, gradual exposure to severe systemic hypoxaemia, in which inspired oxygen is gradually decreased by 1% and maintained at 7% for 2 weeks, results in inhibition of oxidative metabolism, decreased reactive oxygen species production and oxidative DNA damage, and reactivation of cardiomyocyte mitosis. Notably, we find that exposure to hypoxaemia 1 week after induction of myocardial infarction induces a robust regenerative response with decreased myocardial fibrosis and improvement of left ventricular systolic function. Genetic fate-mapping analysis confirms that the newly formed myocardium is derived from pre-existing cardiomyocytes. These results demonstrate that the endogenous regenerative properties of the adult mammalian heart can be reactivated by exposure to gradual systemic hypoxaemia, and highlight the potential therapeutic role of hypoxia in regenerative medicine.
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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.