ArticleJournal of cachexia, sarcopenia and muscle2024
Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization.
Article in Journal of cachexia, sarcopenia and muscle, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07162090 (Observation of the Impact of Hypoxia - Inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients), which is not on this map. Cited by 12 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.
Observation of the Impact of Hypoxia - Inducible Factor Prolyl Hydroxylase Inhibitors on Sarcopenia in Hemodialysis Patients
Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Pathological changes and therapeutic strategies for sarcopenia.EFORT open reviews · 2026Review
- The endocrine product of renal (preglomerular) contractile pericytes depends on prolyl-4-hydroxylases 2 and 3.The Journal of physiology · 2026Article
- Assessing dyspnea severity in chronic obstructive pulmonary disease using intercostal muscle ultrasound/photoacoustic multimodal imaging.Photoacoustics · 2026Article
- Exercise improves hypobaric hypoxia-induced skeletal muscle dysfunction via Sirt1-Mediated myotube and mitochondrial remodeling.Journal of advanced research · 2026Article
- Transient hypoxia followed by progressive reoxygenation is required for muscle repair.EMBO reports · 2026Article
- Temporal dynamics of glomerular and microvascular remodeling in high-altitude renal injury: a structure-function analysis in rats.Frontiers in physiology · 2026Article
- Roles of DRP1 and the fission protein interactome as regulators of cellular stability and sarcopenia in skeletal muscle aging.Aging advances · 2025Article
- Iron Deficiency Impairs Muscle Stem Cell Proliferation and Skeletal Muscle Regeneration via HIF-2α Stabilization.Journal of cachexia, sarcopenia and muscle · 2025Article
- Hypoxia and Tissue Regeneration: Adaptive Mechanisms and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Normal-weight obesity in high-altitude youth: Gender disparities and protective effects of native adaptation.PloS one · 2025Article
- Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization.Journal of cachexia, sarcopenia and muscle · 2024Article
- Mechanisms ofIntegrative cancer therapiesReview
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundChronic hypoxia and skeletal muscle atrophy commonly coexist in patients with COPD and CHF, yet the underlying physio-pathological mechanisms remain elusive. Muscle regeneration, driven by muscle stem cells (MuSCs), holds therapeutic potential for mitigating muscle atrophy. This study endeavours to investigate the influence of chronic hypoxia on muscle regeneration, unravel key molecular mechanisms, and explore potential therapeutic interventions.
methodsExperimental mice were exposed to prolonged normobaric hypoxic air (15% pO
resultsChronic hypoxia led to limb muscle atrophy (EDL: 17.7%, P < 0.001; Soleus: 11.5% reduction in weight, P < 0.001) and weakness (10.0% reduction in peak-isometric torque, P < 0.001), along with impaired muscle regeneration characterized by diminished myofibre cross-sectional areas, increased fibrosis (P < 0.001), and incomplete strength recovery (92.3% of pre-injury levels, P < 0.05). HIF-2α stabilization in MuSC under chronic hypoxia hindered MuSC proliferation (26.1% reduction of MuSC at 10 dpi, P < 0.01). HIF-2α ablation in MuSC mitigated the adverse effects of chronic hypoxia on muscle regeneration and MuSC proliferation (30.9% increase in MuSC numbers at 10 dpi, P < 0.01), while HIF-1α ablation did not have the same effect. HIF-2α stabilization under chronic hypoxia led to elevated local ACE, a novel direct target of HIF-2α. Notably, pharmacological interventions with PT2385 or lisinopril enhanced muscle regeneration under chronic hypoxia (PT2385: 81.3% increase, P < 0.001; lisinopril: 34.6% increase in MuSC numbers at 10 dpi, P < 0.05), suggesting their therapeutic potential for alleviating chronic hypoxia-associated muscle atrophy.
conclusionsChronic hypoxia detrimentally affects skeletal muscle regeneration by stabilizing HIF-2α in MuSC and thereby diminishing MuSC proliferation. HIF-2α increases local ACE levels in skeletal muscle, contributing to hypoxia-induced regenerative deficits. Administration of HIF-2α or ACE inhibitors may prove beneficial to ameliorate chronic hypoxia-associated muscle atrophy and weakness by improving muscle regeneration under chronic hypoxia.
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