ArticleProceedings of the National Academy of Sciences of the United States of America2012
Epigenetic regulation of hypoxic sensing disrupts cardiorespiratory homeostasis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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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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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.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- Effects of early- and mid-life stress on DNA methylation of genes associated with subclinical cardiovascular disease and cognitive impairment: a systematic review.BMC medical genetics · 2019Pooled it
- An epigenetic perspective on neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy.Clinical epigenetics · 2025Review
- Unveiling the molecular and cellular links between obstructive sleep apnea-hypopnea syndrome and vascular aging.Chinese medical journal · 2025Review
- Hypoxia sensing in the body: An update on the peripheral and central mechanisms.Experimental physiology · 2024Review
- Possible Molecular Mechanisms of Hypertension Induced by Sleep Apnea Syndrome/Intermittent Hypoxia.Life (Basel, Switzerland) · 2024Review
- Comparison of hypoxia- and hyperoxia-induced alteration of epigene expression pattern in lungs of Pleurodeles waltl and Mus musculus.PloS one · 2024Article
- Postinspiratory and preBötzinger complexes contribute to respiratory-sympathetic coupling in mice before and after chronic intermittent hypoxia.Frontiers in neuroscience · 2024Article
- Pathophysiological mechanisms and therapeutic approaches in obstructive sleep apnea syndrome.Signal transduction and targeted therapy · 2023Review
- A consequence of immature breathing induces persistent changes in hippocampal synaptic plasticity and behavior: a role of prooxidant state and NMDA receptor imbalance.Frontiers in molecular neuroscience · 2023Article
- Pathogenesis of Bronchopulmonary Dysplasia: Role of Oxidative Stress from 'Omics' Studies.Antioxidants (Basel, Switzerland) · 2022Review
- On the Relationship between Diabetes and Obstructive Sleep Apnea: Evolution and Epigenetics.Biomedicines · 2022Review
- Adaptive cardiorespiratory changes to chronic continuous and intermittent hypoxia.Handbook of clinical neurology · 2022Review
- Time Domains of Hypoxia Responses and -Omics Insights.Frontiers in physiology · 2022Review
- Lysine demethylase KDM6B regulates HIF-1α-mediated systemic and cellular responses to intermittent hypoxia.Physiological genomics · 2021Article
- Epigenetic Alterations in Pediatric Sleep Apnea.International journal of molecular sciences · 2021Review
- Review
- Mechanisms of Ataxia Telangiectasia Mutated (ATM) Control in the DNA Damage Response to Oxidative Stress, Epigenetic Regulation, and Persistent Innate Immune Suppression Following Sepsis.Antioxidants (Basel, Switzerland) · 2021Review
- Epigenetic Blockade of Hippocampal SOD2 Via DNMT3b-Mediated DNA Methylation: Implications in Mild Traumatic Brain Injury-Induced Persistent Oxidative Damage.Molecular neurobiology · 2021Article
- Early Changes and Indicators Characterizing Lung Aging in Neonatal Chronic Lung Disease.Frontiers in medicine · 2021Review
- The Pathophysiology of Rett Syndrome With a Focus on Breathing Dysfunctions.Physiology (Bethesda, Md.) · 2020Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Recurrent apnea with intermittent hypoxia is a major clinical problem in preterm infants. Recent studies, although limited, showed that adults who were born preterm exhibit increased incidence of sleep-disordered breathing and hypertension, suggesting that apnea of prematurity predisposes to autonomic dysfunction in adulthood. Here, we demonstrate that adult rats that were exposed to intermittent hypoxia as neonates exhibit exaggerated responses to hypoxia by the carotid body and adrenal chromaffin cells, which regulate cardio-respiratory function, resulting in irregular breathing with apneas and hypertension. The enhanced hypoxic sensitivity was associated with elevated oxidative stress, decreased expression of genes encoding antioxidant enzymes, and increased expression of pro-oxidant enzymes. Decreased expression of the Sod2 gene, which encodes the antioxidant enzyme superoxide dismutase 2, was associated with DNA hypermethylation of a single CpG dinucleotide close to the transcription start site. Treating neonatal rats with decitabine, an inhibitor of DNA methylation, during intermittent hypoxia exposure prevented oxidative stress, enhanced hypoxic sensitivity, and autonomic dysfunction. These findings implicate a hitherto uncharacterized role for DNA methylation in mediating neonatal programming of hypoxic sensitivity and the ensuing autonomic dysfunction in adulthood.
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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.